Dimethylformamide → 2-(4-Fluoro-phenyl)-N-((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-acetamide

HRID 604898Notes

Reaction equation

HRID 604898 reaction equation
Cl.Cl.Cl.[NH2:4][C@H:5]([C:10]1[N:11]=[C:12]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]3)=[C:18]([O:28][CH3:29])[CH:17]=2)[S:13][CH:14]=1)[CH2:6][CH:7]([CH3:9])[CH3:8].[F:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38](O)=[O:39])=[CH:33][CH:32]=1.CN(C=O)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>[OH-].[Na+]>[F:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]([NH:4][C@H:5]([C:10]2[N:11]=[C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]4)=[C:18]([O:28][CH3:29])[CH:17]=3)[S:13][CH:14]=2)[CH2:6][CH:7]([CH3:8])[CH3:9])=[O:39])=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 98372-(4-Fluorophenyl)acetic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86624689[4-((S)-1-amino-3-methyl-butyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine trihydrochloride

Product 1

HCID 866246932-(4-Fluoro-phenyl)-N-((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-acetamide

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 96 mg (0.2 mmol) [4-((S)-1-amino-3-methyl-butyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine trihydrochloride and of 35 mg (0.22 mmol) 4-fluorophenylacetic acid in DMF (2 ml) 121 mg (1.2 mmol) N-methyl morpholine and 114 mg (0.3 mmol) HBTU (O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate) were added. The reaction was stirred over night at room temperature. The reaction was diluted with 2N aqueous NaOH solution (6 ml) and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulphate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 95 mg (94%) of 2-(4-fluoro-phenyl)-N—((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-acetamide as a yellow solid. MS ISP (m/e): 508.0 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm) 10.38 (s, 1H), 8.30 (d, 1H), 7.96 (d, 1H), 7.89 (s, 1H), 7.65 (s, 1H), 7.30-7.20 (m, 3H), 7.15-6.97 (m, 4H), 6.54 (s, 1H), 4.60 (m, 1H), 3.80 (s, 3H), 3.45 (m, 2H), 2.14 (s, 3H), 1.69-1.48 (m, 3H), 0.92 (d, 3H), 0.85 (d, 3H).

Workup

  1. extractionextracted twice with ethyl acetate
  2. dry with materialThe combined organic layers were dried over sodium sulphate
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. customThe crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 95 mg (94%) of 2-(4-fluoro-phenyl)-N—((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-acetamide as a yellow solid

Sources & evidence

ORD record
ord-654d02e14bef4f59becf62f4c60db0c2
Source dataset
uspto-grants-2011_03
Patent number
US07910740B2

Reaction notes

Loading…