Dimethylformamide → 2-(4-Fluorophenyl)-1-(2-((3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)amino)-6,7-dihydrothiazolo[5,4-c]pyridin-5(4H)-yl)ethanone

HRID 604913Notes

Reaction equation

HRID 604913 reaction equation
Cl.Cl.Cl.[CH3:4][O:5][C:6]1[CH:7]=[C:8]([NH:18][C:19]2[S:20][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:26]=3[N:27]=2)[CH:9]=[CH:10][C:11]=1[N:12]1[CH:16]=[C:15]([CH3:17])[N:14]=[CH:13]1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36](O)=[O:37])=[CH:31][CH:30]=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:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]([N:23]2[CH2:24][CH2:25][C:26]3[N:27]=[C:19]([NH:18][C:8]4[CH:9]=[CH:10][C:11]([N:12]5[CH:16]=[C:15]([CH3:17])[N:14]=[CH:13]5)=[C:6]([O:5][CH3:4])[CH:7]=4)[S:20][C:21]=3[CH2:22]2)=[O:37])=[CH:31][CH:30]=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 25106280N-(3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-amine trihydrochloride

Product 1

HCID 735550512-(4-Fluorophenyl)-1-(2-((3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)amino)-6,7-dihydrothiazolo[5,4-c]pyridin-5(4H)-yl)ethanone

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 90 mg (0.2 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-(4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-amine trihydrochloride and 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 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 70 mg (73%) 2-(4-fluoro-phenyl)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl}-ethanone as a yellow viscous oil. MS ISP (m/e): 478.0 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.32 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.32-7.24 (m, 4H), 7.30 (d, 1H), 7.24 (d, 1H), 7.02 (s, 1H), 4.65 & 4.55 (br s, 2H), 3.84 (m, 2H), 3.78 (s, 3H), 2.89 (s, 2H), 2.62 (m, 2H), 2.14 (s, 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 70 mg (73%) 2-(4-fluoro-phenyl)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl}-ethanone as a yellow viscous oil

Sources & evidence

ORD record
ord-43d7b8e88ebe471ab49e6eb12ec13f04
Source dataset
uspto-grants-2011_03
Patent number
US07910740B2

Reaction notes

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