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

반응식

HRID 1594482 반응식
[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

참가 물질

5

반응물 3

HCID 27732391-Benzyl-1H-imidazole-5-carboxaldehyde2회HCID 5049666Sodium triacetoxyborohydride2회HCID 21865046N-(4-(6-(2-Amino-4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

생성물 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

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

반응 조건

온도
25 °C

실험 절차

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.

후처리

  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]

출처 및 근거

ORD 기록
ord-312c7ac7445445a7bd5dc73bb373d630
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07301022B2

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