一种具有季碳中心的吡唑啉核苷类似物的合成方法与流程

文档序号:15885765发布日期:2018-11-09 18:51阅读:236来源:国知局

本发明涉及嘌呤核苷类似物的合成,具体涉及一种具有季碳中心的吡唑啉核苷类似物的合成方法,属于有机化学中的有机合成领域。

背景技术

含有季碳中心的吡唑啉类化合物在许多生物活性分子中普遍存在。对于这样的吡唑啉化合物代表性的例子有:在市销售的除草安全剂吡唑解草酯,杀虫剂rh3421,以及具有良好的抗疟活性的氯代奎宁吡唑啉等。因此,构建具有季碳中心的吡唑啉是非常具有应用前景的。

利用重氮酯的1,3-偶极环加成反应合成吡唑啉是非常经典的合成方法。烯烃或炔烃与烷基重氮或重氮乙酸酯的环加成反应已经有了非常多的报道。然而,与此相比,联烯这类累积双键化合物与重氮化合物进行1.3-偶极环加成的报道还是比较罕见的。同时,含有季碳中心的吡唑啉合成也是很少有文献公开报道。



技术实现要素:

为克服上述缺陷,本发明采用以9-联烯嘌呤和α-烷基/芳基重氮乙酸酯为原料,加入溶剂,以dppb/pd2(dba)3催化剂合成吡唑啉核苷类似物。该方法反应后得到了新型的吡唑啉核苷类似物,并提供了两种途径控制吡唑啉核苷类似物,提供了该类化合物的多样性以及方法学控制上的单一性。

一种具有季碳中心的吡唑啉核苷类似物的合成方法,其特征在于,包括如下操作:以9-联烯嘌呤1和α-烷基/芳基重氮乙酸酯2为原料,加入溶剂,在dppb或pd2(dba)3催化剂的存在下,反应得到吡唑啉核苷类似物3,反应方程式如下:

其中,r3选自h、cl,r2选自ome、oet、cl、nme2、net2、r选自me、et、n-c5h11、ph;r1选自me、et、i-pr、t-bu。

进一步地,当r3=h时,r2代表下列基团中的一种:ome、oet、cl、net2、当r3=cl时,r2代表下列基团中的一种:oet、nme2;r代表下列基团中的一种:me、et、n-c5h11、ph;r1代表下列基团中的一种:me、et、i-pr、t-bu。

进一步地,在上述技术方案中,所述催化剂取自dppb或者pd2(dba)3。

进一步地,在上述技术方案中,当所需产物主要为1-吡唑啉时,选择催化剂为pd2(dba)3;其中,9-联烯嘌呤1、α-烷基/芳基重氮乙酸酯2、pd2(dba)3催化剂的摩尔比为1:4-6:0.1;

当所需产物主要为多种吡唑啉时,选择催化剂为dppb;其中,9-联烯嘌呤1、α-烷基/芳基重氮乙酸酯2、dppb催化剂的摩尔比为1:4-6:0.2。

进一步地,在上述技术方案中,反应溶剂选自甲苯、1,2-二氯乙烷、三氟甲苯或均三甲苯。

进一步地,在上述技术方案中,反应温度选自60℃至100℃。

进一步地,在上述技术方案中,整个反应过程需要惰性气体保护下操作,惰性气体优选氮气。

在上述反应条件下,经过反应纯化后,对于不同的产物分离收率可达47%-91%。

进一步地,在上述技术方案中得到的产物3,可以进一步衍生。无论是e-式或者是z-式的产物3,均可通过钯碳加氢反应得到前所未有的单一的氢化产物5。

反应方程式如下:

进一步地,在上述技术方案中,所述催化剂取自钯碳催化剂。

进一步地,在上述技术方案中,反应溶剂选自甲醇。

进一步地,在上述技术方案中,反应温度选自常温。

进一步地,在上述技术方案中,整个反应过程需要氢气作为氢源。

在上述反应条件下,经过反应纯化后,对于氢化产物收率可达95%。

发明有益效果:

本发明公开了新型具有季碳中心的吡唑啉核苷类似物,以9-联烯嘌呤1和α-烷基/芳基重氮乙酸酯2为原料,通过两种不同的方法来进行合成,其中采用pd2(dba)3催化剂时得到的产物单一。采用dppb催化剂时,得到了除主要产物之外异构体的产物,即通过催化剂的选择来控制吡唑啉产物的多样性与单一性。

具体实施方式

实施例1

aunlessotherwisenoted,reactionconditionswere:cat.(20mol%),1a(0.05mmol),2a(0.3mmol)insolvent(1.0ml)undern2for48h.btotalyieldof3aaand4aa.cisolatedyield.ddeterminedby1hnmrspectroscopyofthecrudereactionmixture.e2aandpd2(dba)3wereaddedfortwotimesinmesitylene.

在反应条件的筛选过程中,首先考察了催化剂对反应的影响(entries1-6,9-14),确定了dppb为得到多种吡唑啉的最佳催化剂,pd2(dba)3为得到单一1-吡唑啉最佳催化剂。

在其它条件固定的情况下,仅考察溶剂对反应的影响(entries15-17),确定了甲苯为得到多种吡唑啉的最佳溶剂,均三甲苯为合成1-吡唑啉最佳溶剂。

在其它条件固定的情况下,仅考察反应温度对反应的影响(entries3,7-8,17-18),确定了100℃为最佳温度。

实施例2

以1a和2a化合物为例,该反应在pd2(dba)3催化下的反应步骤如下:

称量9.4mg(0.05mmol,1equiv)化合物1a放于15ml干净的反应管中,然后加入2.3mg的pd2(dba)3(0.005mmol,5%)催化剂。将反应管密封,通过三通管将反应瓶中的空气抽空,然后通入氮气,称量19.2mg的化合物2a(0.15mmol,3equiv)并溶于均三甲苯溶液1ml中,用注射器加入反应中,并且使反应完全在氮气条件下,100摄氏度进行。待反应24小时后,再次注射2.3mg的pd2(dba)3(0.005mmol,5%)催化剂,19.2mg的化合物2a(0.15mmol,3equiv)在均三甲苯溶剂中,继续反应24小时。用tcl检测发现原料基本消失。将反应液取出,用真空旋转蒸发仪将溶液中溶剂旋干,利用薄层层析分离的方法,用石油醚与乙酸乙酯为3:1的展开体系,分离。称量产物3aa为7.5mg,产率为73%。1hnmr(400mhz,cdcl3)δ8.66(s,1h),8.60(t,j=2.4hz,1h),8.25(s,1h),4.33-4.25(m,2h),4.24(s,3h),3.32(dd,j=16.8,2.4hz,1h),2.61(dd,j=16.8,2.4hz,1h),1.70(s,3h),1.33(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ169.9,161.6,153.8,153.5,151.6,139.0,122.7,121.5,94.4,62.6,54.8,33.5,23.0,14.2.

hrms:exactmasscalcdforc14h16n6o3na(m+na+)requiresm/z339.1182,foundm/z339.1180.

按照上述反应条件,改变反应底物,结果如下:

实施例3:

以1a和2a化合物为例,该反应在双(二苯基膦)丁烷dppb催化下的反应步骤如下:

称量18.8mg(0.1mmol,1equiv)化合物1a放于20ml干净的反应管中,然后加入8.5mg的dppb(0.02mmol,20%)催化剂。将反应管密封,通过三通管将反应瓶中的空气抽空,然后通入氮气,称量38.4mg的化合物2a(0.3mmol,3equiv)并溶于甲苯溶液1.5ml中,用注射器加入反应中,并且使反应完全在氮气条件下,100摄氏度,进行。待反应48小时后,用tcl检测发现原料基本消失。将反应液取出,用真空旋转蒸发仪将溶液中溶剂旋干,利用柱层析的方法,石油醚与乙酸乙酯为3:1的展开体系,过柱分离。旋干溶液,得到产物3aa与4aa分别为10.7mg、18.0mg,产率为34%和57%。

(e)-ethyl5-((6-methoxy-9h-purin-9-yl)methylene)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(3aa)

1hnmr(400mhz,cdcl3)δ8.66(s,1h),8.60(t,j=2.4hz,1h),8.25(s,1h),4.33-4.25(m,2h),4.24(s,3h),3.32(dd,j=16.8,2.4hz,1h),2.61(dd,j=16.8,2.4hz,1h),1.70(s,3h),1.33(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ169.9,161.6,153.8,153.5,151.6,139.0,122.7,121.5,94.4,62.6,54.8,33.5,23.0,14.2.

hrms:exactmasscalcdforc14h16n6o3na(m+na+)requiresm/z339.1182,foundm/z339.1180.

(z)-ethyl4-((6-methoxy-9h-purin-9-yl)methylene)-5-methyl-4,5-dihydro-1h-pyrazole-5-carboxylate(4aa)

1hnmr(600mhz,cdcl3)δ8.60(s,1h),8.14(s,1h),7.45(s,1h),7.07(s,1h),6.84(s,1h),4.37-4.29(m,2h),4.21(s,3h),1.74(s,3h),1.34(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ171.8,161.5,153.2,151.5,140.5,137.5,135.9,121.4,112.3,63.0,54.7,26.4,14.2.

hrms:exactmasscalcdforc14h16n6o3na(m+na+)requiresm/z339.1182,foundm/z339.1178.

按照上述反应条件,改变反应底物,结果如下:

areactionconditions:dppb(20mol%),1a(0.1mmol),2a-2g(0.6mmol)intoluene(1ml)undern2for48hours.btotalyieldof3and4.cisolatedyields.werereportddeterminedby1hnmrspectroscopyofthecrudereactionmixture.

(e)-ethyl5-((6-ethoxy-9h-purin-9-yl)methylene)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(3ba)

1hnmr(400mhz,cdcl3)δ8.61(s,1h),8.58(t,j=2.4hz,1h),8.22(s,1h),4.70(q,j=7.2hz,2h),4.27(q,j=7.2hz,2h),3.30(dd,j=16.8,2.4hz,1h),2.60(dd,j=16.8,2.4hz,1h),1.69(s,3h),1.53(t,j=7.2hz,3h),1.31(t,j=7.2hz,3h).

13cnmr(100mhz,cdcl3)δ169.8,161.3,153.6,153.4,151.6,138.7,122.7,121.3,94.3,63.7,62.5,33.3,22.8,14.5,14.1.

hrms:exactmasscalcdforc15h18n6o3na(m+na+)requiresm/z353.1338,foundm/z353.1333.

(z)-ethyl4-((6-ethoxy-9h-purin-9-yl)methylene)-5-methyl-4,5-dihydro-1h-pyrazole-5-carboxylate(4ba)

1hnmr(400mhz,cdcl3)δ8.58(s,1h),8.13(s,1h),7.46(s,1h),7.07(s,1h),6.84(s,1h),4.70(q,j=7.2hz,2h),4.29(q,j=7.2hz,2h),1.75(s,3h),1.53(t,j=7.2hz,3h),1.34(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ171.8,161.3,153.2,151.6,140.3,137.5,135.8,121.3,112.3,69.3,63.7,63.0,26.3,14.6,14.2.

hrms:exactmasscalcdforc15h18n6o3na(m+na+)requiresm/z353.1338,foundm/z353.1341.

(e)-ethyl5-((6-chloro-9h-purin-9-yl)methylene)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(3ca)

1hnmr(600mhz,cdcl3)δ8.87(s,1h),8.55(s,1h),8.42(s,1h),4.31-4.23(m,2h),3.32(d,j=17.4hz,1h),2.61(d,j=17.4hz,1h),1.70(s,3h),1.32(t,j=6.6hz,3h).

13cnmr(150mhz,cdcl3)δ169.7,150.0,153.3,152.4,151.3,142.0,131.7,122.1,94.9,62.8,33.4,22.9,14.2.

hrms:exactmasscalcdforc13h13cln6o2na(m+na+)requiresm/z343.0686,foundm/z343.0680.

(z)-ethyl4-((6-chloro-9h-purin-9-yl)methylene)-5-methyl-4,5-dihydro-1h-pyrazole-5-carboxylate(4ca)

1hnmr(600mhz,cdcl3)δ8.82(s,1h),8.33(s,1h),7.39(s,1h),7.04(s,1h),6.91(s,1h),4.30(q,j=6.6hz,2h),1.75(s,3h),1.35(t,j=6.6hz,3h).

13cnmr(150mhz,cdcl3)δ171.3,152.9,151.9,151.1,143.4,137.4,136.6,131.3,111.1,69.4,63.0,26.3,14.0.

hrms:exactmasscalcdforc13h14cln6o2(m+h+)requiresm/z321.0867,foundm/z321.0861.

(e)-ethyl5-((6-(diethylamino)-9h-purin-9-yl)methylene)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(3da)

1hnmr(400mhz,cdcl3)δ8.57(t,j=2.4hz,1h),8.40(s,1h),8.04(s,1h),4.31-4.22(m,2h),4.00(s,4h),3.25(dd,j=16.8,2.4hz,1h),2.54(dd,j=16.8,2.4hz,1h),1.67(s,3h),1.31(td,j=7.2,2.8hz,3h).

13cnmr(150mhz,cdcl3)δ170.1,165.2,163.3,154.0,153.8,152.8,134.9,123.3,94.0,62.5,42.7,33.4,23.0,14.2,6.6.

hrms:exactmasscalcdforc17h23n7o2na(m+na+)requiresm/z380.1811,foundm/z380.1808.

(z)-ethyl4-((6-(diethylamino)-9h-purin-9-yl)methylene)-5-methyl-4,5-dihydro-1h-pyrazole-5-carboxylate(4da)

1hnmr(400mhz,cdcl3)δ8.38(s,1h),7.96(s,1h),7.46(s,1h),7.09(s,1h),6.79(s,1h),4.28(q,j=7.2hz,2h),3.99(s,4h),1.73(s,3h),1.31(t,j=7.2hz,9h).

13cnmr(150mhz,cdcl3)

hrms:exactmasscalcdforc17h23n7o2na(m+na+)requiresm/z380.1811,foundm/z380.1817.

(e)-ethyl3-methyl-5-((6-(piperidin-1-yl)-9h-purin-9-yl)methylene)-4,5-dihydro-3h-pyrazole-3-carboxylate(3ea)

1hnmr(400mhz,cdcl3)δ8.56(s,1h),8.39(s,1h),8.02(s,1h),4.43-4.10(m,6h),3.24(dd,j=16.8,2.4hz,1h),2.53(dd,j=16.8,2.4hz,1h),1.72(t,j=6.4hz,6h),1.67(s,3h),1.31(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ170.1,154.1,153.7,152.9,150.9,134.5,123.2,119.5,94.1,62.6,46.5,33.3,26.3,24.9,23.0,14.2.

hrms:exactmasscalcdforc18h23n7o2na(m+na+)requiresm/z392.1811,foundm/z392.1814.

(z)-ethyl5-methyl-4-((6-(piperidin-1-yl)-9h-purin-9-yl)methylene)-4,5-dihydro-1h-pyrazole-5-carboxylate(4ea)

1hnmr(400mhz,cdcl3)δ8.37(s,1h),7.95(s,1h),7.44(s,1h),7.08(s,1h),6.80(s,1h),4.22-4.29(m,6h),1.76-1.68(m,9h),1.32(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ172.0,154.0,153.5,150.6,137.8,136.0,134.4,119.4,113.0,69.3,62.9,46.7,26.3,26.2,24.9,14.2.

hrms:exactmasscalcdforc18h23n7o2na(m+na+)requiresm/z392.1811,foundm/z392.1818.

(e)-ethyl3-methyl-5-((6-morpholino-9h-purin-9-yl)methylene)-4,5-dihydro-3h-pyrazole-3-carboxylate(3fa)

1hnmr(600mhz,cdcl3)δ8.57(s,1h),8.43(s,1h),8.03(s,1h),4.35-4.22(m,4h),3.85(s,4h),3.26(d,j=16.8hz,1h),2.54(d,j=16.8hz,1h),1.68(s,3h),1.32(t,j=6.6hz,3h).

13cnmr(100mhz,cdcl3)δ170.1,154.1,153.6,153.2,151.0,135.1,123.1,119.7,94.2,67.1,62.6,45.8,33.4,23.0,14.2.

hrms:exactmasscalcdforc17h21n7o3na(m+na+)requiresm/z394.1604,foundm/z394.1596.

(z)-ethyl5-methyl-4-((6-morpholino-9h-purin-9-yl)methylene)-4,5-dihydro-1h-pyrazole-5-carboxylate(4fa)

1hnmr(600mhz,cdcl3)δ8.42(s,1h),7.97(s,1h),7.41(s,1h),7.07(s,1h),6.82(s,1h),4.32-4.27(m,4h),3.85(s,4h),1.74(s,3h),1.33(t,j=6.6hz,3h).

13cnmr(150mhz,cdcl3)δ171.9,154.1,153.4,150.8,137.6,136.6,134.9,119.6,112.8,69.3,67.2,63.0,45.8,26.3,14.2.

hrms:exactmasscalcdforc17h21n7o3na(m+na+)requiresm/z394.1604,foundm/z394.1611

(e)-ethyl5-((2-chloro-6-(dimethylamino)-9h-purin-9-yl)methylene)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(3ga)

1hnmr(400mhz,cdcl3)δ8.49(t,j=2.4hz,1h),7.98(s,1h),4.32-4.18(m,2h),3.75(s,3h),3.46-3.15(m,4h),2.50(dd,j=16.8,2.4hz,1h),1.66(s,3h),1.31(t,j=7.2hz,3h).

13cnmr(100mhz,cdcl3)δ170.0,155.3,155.0,153.4,151.5,135.1,122.9,118.8,94.2,62.6,39.4,33.2,22.9,14.2,8.7.

hrms:exactmasscalcdforc15h18cln7o2na(m+na+)requiresm/z386.1108,foundm/z386.1113

(z)-ethyl4-((2-chloro-6-(dimethylamino)-9h-purin-9-yl)methylene)-5-methyl-4,5-dihydro-1h-pyrazole-5-carboxylate(4ga)

1hnmr(600mhz,cdcl3)δ7.90(s,1h),7.39(s,1h),7.02(s,1h),6.81(s,1h),4.28(q,j=6.4hz,2h),3.75(s,3h),3.31(s,3h),1.72(s,3h),1.34(t,j=6.8hz,3h).

13cnmr(150mhz,cdcl3)δ171.8,155.3,154.9,151.4,137.3,136.6,135.0,118.7,112.7,69.4,63.0,38.2,26.1,14.1.

hrms:exactmasscalcdforc15h18cln7o2na(m+na+)requiresm/z386.1108,foundm/z386.1101

(e)-iso-propyl3-ethyl-5-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-3h-pyrazole-3-carboxylate(3ab)

1hnmr(600mhz,cdcl3)δ8.65(s,1h),8.57(s,1h),8.28(s,1h),5.1-5.2(m,1h),4.23(s,3h),3.26(d,j=17.2hz,1h),2.62(d,j=17.2hz,1h),2.33–2.26(m,1h),1.9-2.0(m,1h),1.32(dd,j=17.8,6.4hz,6h),0.92(t,j=7.2hz,3h).

13cnmr(100mhz,cdcl3)δ169.0,161.6,153.9,153.5,151.7,139.0,122.5,121.5,99.6,70.4,54.7,30.0,29.6,21.8,21.8,8.4.

hrms:exactmasscalcdforc16h20n6o3na(m+na+)requiresm/z367.1495,foundm/z367.1485.

(z)-iso-propyl5-ethyl-4-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-1h-pyrazole-5-carboxylate(4ab)

1hnmr(400mhz,cdcl3)δ8.60(s,1h),8.13(s,1h),7.40(s,1h),7.04(s,1h),6.84(s,1h),5.17–5.02(m,1h),4.22(s,3h),2.17(s,1h),2.0-2.1(m,1h),1.9-2.0(m,1h),1.33(t,j=5.2hz,6h),0.99(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ170.8,161.5,153.1,151.6,140.5,137.6,135.0,112.2,73.3,70.9,54.6,33.6,29.8,21.8,21.7,8.6.

hrms:exactmasscalcdforc16h20n6o3na(m+na+)requiresm/z367.1495,foundm/z367.1489.

(e)-tert-butyl3-ethyl-5-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-3h-pyrazole-3-carboxylate(3ac)

1hnmr(600mhz,cdcl3)δ8.64(s,1h),8.56(s,1h),8.28(s,1h),4.23(s,3h),3.23(d,j=17.2hz,1h),2.57(d,j=17.2hz,1h),2.25-2.32(m,1h),1.92-1.97(m,1h),1.51(s,9h),0.92(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ170.3,161.5,153.2,151.6,140.4,137.6,135.1,121.3,112.1,84.0,73.7,54.6,33.7,28.0,8.6.

hrms:exactmasscalcdforc17h22n6o3na(m+na+)requiresm/z381.1651,foundm/z381.1647.

(z)-tert-butyl5-ethyl-4-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-1h-pyrazole-5-carboxylate(4ac)

1hnmr(600mhz,cdcl3)δ8.59(s,1h),8.13(s,1h),7.39(s,1h),7.02(s,1h),6.83(s,1h),14.21(s,3h),2.03-2.10(m,1h),1.89-1.96(m,1h),1.53(s,9h),0.98(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ170.3,161.5,153.2,151.6,140.4,137.6,135.1,121.3,112.1,84.0,73.7,54.6,33.7,28.0,8.60.

hrms:exactmasscalcdforc17h22n6o3na(m+na+)requiresm/z381.1651,foundm/z381.1654.

(e)-methyl3-ethyl-5-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-3h-pyrazole-3-carboxylate(3ad)

1hnmr(600mhz,cdcl3)δ8.65(s,1h),8.58(s,1h),8.27(s,1h),4.23(s,3h),3.84(s,3h),3.27(d,j=17.2hz,1h),2.66(d,j=17.2hz,1h),2.26-2.32(m,1h),2.07-2.20(m,1h),0.92(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ169.9,161.6,153.8,153.5,151.6,139.0,122.7,121.5,94.4,62.6,54.8,33.5,23.0,14.2.

hrms:exactmasscalcdforc14h16n6o3na(m+na+)requiresm/z339.1182,foundm/z339.1188.

(z)-methyl5-ethyl-4-((6-methoxy-9h-purin-9-yl)methylene)-4,5-dihydro-1h-pyrazole-5-carboxylate(4ad)

1hnmr(600mhz,cdcl3)δ8.60(s,1h),8.13(s,1h),7.42(s,1h),7.04(s,1h),6.82(s,1h),4.21(s,3h),3.85(s,3h),2.11-2.16(m,1h),1.95-2.01(m,1h),0.98(t,j=7.2hz,3h).

13cnmr(150mhz,cdcl3)δ172.0,161.5,153.2,151.5,140.6,137.6,134.6,121.3,112.4,73.4,54.6,53.8,33.5,8.6.

hrms:exactmasscalcdforc14h16n6o3na(m+na+)requiresm/z339.1182,foundm/z339.1186.

实施例4:

以6-甲氧基嘌呤产物3aa为例,衍生步骤如下:

称量3aa(0.1mmol,31.6mg),转移至一个洁净的15ml反应管中,加入2ml甲醇,称量0.2当量的钯/碳试剂(0.02mmol,2.12mg),转移至反应管中,反应体系置换氢气,并插上氢气球,保持一定压力。常温下反应3小时,反应结束,3aa完全转化,仅有一个产物。过硅藻土除去钯/碳,柱层析分离。得到产物7aa,产量30.2mg,产率为95%。

ethyl5-((6-methoxy-9h-purin-9-yl)methyl)-3-methyl-4,5-dihydro-3h-pyrazole-3-carboxylate(5aa)

1hnmr(400mhz,cdcl3)δ8.55(s,1h),7.95(s,1h),5.06(s,2h),4.12-4.19(m,6h),3.14(d,j=17.2hz,1h),2.50(d,j=17.2hz,1h),1.46(s,3h),1.21(d,j=7.2hz,3h).

13cnmr(100mhz,cdcl3)δ174.7,161.4,152.5,152.1,149.0,142.1,77.5,69.2,62.2,54.5,43.1,42.8,23.9,14.2.

hrms:exactmasscalcdforc14h18n6o3na(m+na+)requiresm/z341.1338,foundm/z341.1333.

以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解,本发明不受上述实施例的限制,上述实施例和说明书中描述的只是说明本发明的原理,在不脱离本发明原理的范围下,本发明还会有各种变化和改进,这些变化和改进均落入本发明保护的范围内。

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