聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → (R)-4-(1-(4-cyclopropoxy-6-(2-cyclopropylethynyl)pyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide

HRID 42367

反应方程式

HRID 42367 反应方程式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[C:7]([NH:16][CH:17]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH3:18])[N:8]=[C:9]([O:12][CH:13]3[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[C:29]([CH:31]1[CH2:33][CH2:32]1)#[CH:30].O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH:13]1([O:12][C:9]2[C:10]3[N:11]=[C:2]([C:30]#[C:29][CH:31]4[CH2:33][CH2:32]4)[CH:3]=[CH:4][C:5]=3[N:6]=[C:7]([NH:16][C@@H:17]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH3:18])[N:8]=2)[CH2:15][CH2:14]1

参与物

7

反应物 3

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 138823环丙乙炔HCID 767384494-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide

产物 1

HCID 58275408(R)-4-(1-(4-cyclopropoxy-6-(2-cyclopropylethynyl)pyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide收率 77.7%

试剂、催化剂与溶剂 3

HCID 24350碘化亚铜催化剂HCID 178418476HCID 178418476，化合物催化剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
80 °C

实验过程

A mixture of 4-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide (300 mg, 0.71 mmol), PdCl2(PPh3)2 (25 mg, 0.035 mmol), CuI (13.5 mg, 0.07 mmol) in TEA (1 mL) and DMF (5 mL) was degassed for 10 min then purged with argon. Ethynyl-cyclopropane (0.3 mL, 3.5 mmol) was added and the reaction tube was sealed and heated at 80° C. for 3 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with 5% LiCl solution and brine. Solvent was removed by concentration in vacuo and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, to provide 248 mg (62%) of desired product. MS (m/z) 450.0 [M+H]+; HPLC Rt=2.16 min.

后处理

  1. customwas degassed for 10 min
  2. customthen purged with argon
  3. customthe reaction tube was sealed
  4. temperatureAfter cooling to room temperature
  5. extractionextracted twice with EtOAc
  6. washThe combined organic layers were washed with 5% LiCl solution and brine
  7. customSolvent was removed by concentration in vacuo
  8. customthe residue was purified by RP HPLC

来源与证据

ORD记录
ord-675049cfd59f4a7eba02f6414bc4cfb3
来源数据集
uspto-grants-2013_09
专利号
US08536187B2

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