1-羟基苯并三唑(HOBT) → N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamide

HRID 517543

反应方程式

HRID 517543 反应方程式
[CH3:1][C:2]1[N:3]=[C:4]([C:21](O)=[O:22])[S:5][C:6]=1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:9]=1.[NH2:24][CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:26][OH:27].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O>[OH:27][CH2:26][CH:25]([NH:24][C:21]([C:4]1[S:5][C:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N:14]3[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]3)[CH:9]=2)=[C:2]([CH3:1])[N:3]=1)=[O:22])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

参与物

7

反应物 4

HCID 757711-羟基苯并三唑(HOBT)HCID 92466D-苯甘氨醇HCID 27239391-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐HCID 867114824-Methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylic acid

产物 1

HCID 86711483N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamide收率 48.1%

试剂、催化剂与溶剂 2

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
50 °C

实验过程

To a mixture of 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylic acid (200 mg, 0.6 mmol), 2-amino-2-phenylethanol (99 mg, 0.7 mmol) and TEA (0.3 mL, 1.8 mmol) in DMF (2 mL), EDCI.HCl (175 mg, 0.9 mmol) and HOBT (95 mg, 0.7 mmol) were added. The mixture was stirred at 50° C. overnight, then cooled to RT, diluted with H2O (50 mL) and extracted with DCM/MeOH (10/1, 4×30 mL). The combined organic layers were washed with a saturated aqueous solution of LiCl (3×20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by Combiflash reverse phase chromatography (50%˜60% MeCN/H2O containing 10 mM NH4HCO3) to afford N-(2-hydroxy-1-phenylethyl)-4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxamide as a colorless oil (130 mg, 48%). MS (ES+) C25H30N4O2S requires: 450, found: 451 [M+H]+.

后处理

  1. additionwere added
  2. temperaturecooled to RT
  3. extractionextracted with DCM/MeOH (10/1, 4×30 mL)
  4. washThe combined organic layers were washed with a saturated aqueous solution of LiCl (3×20 mL) and brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product, which
  9. customwas purified by Combiflash reverse phase chromatography (50%˜60% MeCN/H2O containing 10 mM NH4HCO3)

来源与证据

ORD记录
ord-044858c0874c4bf38b404f776ddc9243
来源数据集
uspto-grants-2015_08
专利号
US09115120B2

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