1-Benzyl-1H-imidazole-5-carboxaldehyde → N-(4-(6-(2-((1-Benzyl-1H-imidazol-5-yl)methylamino)-4-(trifluoromethyl)-phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

HRID 1594482

反応式

HRID 1594482 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[N:17]=[CH:16][N:15]=[C:14]([O:18][C:19]2[C:24]3[N:25]=[C:26]([NH:28][C:29](=[O:31])[CH3:30])[S:27][C:23]=3[CH:22]=[CH:21][CH:20]=2)[CH:13]=1.[CH2:32]([N:39]1[C:43]([CH:44]=O)=[CH:42][N:41]=[CH:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:32]([N:39]1[C:43]([CH2:44][NH:1][C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:5]=[CH:4][C:3]=2[C:12]2[N:17]=[CH:16][N:15]=[C:14]([O:18][C:19]3[C:24]4[N:25]=[C:26]([NH:28][C:29](=[O:31])[CH3:30])[S:27][C:23]=4[CH:22]=[CH:21][CH:20]=3)[CH:13]=2)=[CH:42][N:41]=[CH:40]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

参加物

5

反応物 3

HCID 27732391-Benzyl-1H-imidazole-5-carboxaldehyde2 回HCID 5049666Sodium triacetoxyborohydride2 回HCID 21865046N-(4-(6-(2-Amino-4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

生成物 1

HCID 58691321N-(4-(6-(2-((1-Benzyl-1H-imidazol-5-yl)methylamino)-4-(trifluoromethyl)-phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
25 °C

実験手順

A mixture of N-(4-(6-(2-amino-4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)-acetamide (0.20 g, 0.45 mmol, prepared as described in WO04014871) and 1-benzyl-1H-imidazole-5-carbaldehyde (0.21 g, 1.1 mmol, Combi-Blocks) in 1,2-dichloroethane (4 mL) was stirred for 24 h at 25° C. Sodium triacetoxy-borohydride (0.24 g, 1.1 mmol) was added and the mixture was stirred for 4 d at 25° C. Additional amounts of 1-benzyl-1H-imidazole-5-carbaldehyde (0.21 g, 1.1 mmol, Combi-Blocks) and sodium triacetoxyborohydride (0.24 g, 1.1 mmol) were added, and the mixture was stirred for 24 h at 25° C. The mixture was partitioned between H2O and EtOAc, the organic phase was separated, washed with H2O and brine, dried over Na2SO4, and filtered. The filtrate was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [gradient: 0.5-2.2% MeOH (2 M in NH3)/CH2Cl2] to give the title compound as a yellow solid. MS (ESI, pos. ion) m/z: 616 (M+1). Mp: 264.0-264.1° C.

後処理

  1. stirringthe mixture was stirred for 4 d at 25° C
  2. stirringthe mixture was stirred for 24 h at 25° C
  3. customThe mixture was partitioned between H2O and EtOAc
  4. customthe organic phase was separated
  5. washwashed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe filtrate was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography [gradient: 0.5-2.2% MeOH (2 M in NH3)/CH2Cl2]

出典と根拠

ORDレコード
ord-312c7ac7445445a7bd5dc73bb373d630
出典データセット
uspto-grants-2007_11
特許番号
US07301022B2

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