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

Reaction equation

HRID 1594482 reaction equation
[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

Participants

5

Reactant 3

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

Product 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

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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]

Sources & evidence

ORD record
ord-312c7ac7445445a7bd5dc73bb373d630
Source dataset
uspto-grants-2007_11
Patent number
US07301022B2

Linked notes

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