Diisopropylethylamine → 2-methylpropyl 6-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate

HRID 473900Notes

Reaction equation

HRID 473900 reaction equation
FC(F)(F)C(O)=O.[O:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:20]=[C:21]4[N:27]([C:28]([O:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[O:29])[CH:26]=[N:25][C:22]4=[N:23][CH:24]=3)=[CH:18][C:13]=2[CH2:12][NH:11][CH2:10][CH2:9]1.[F:35][C:36]1[CH:37]=[C:38]([CH:42]2[CH2:47][C:46](=[O:48])[CH2:45][CH2:44][N:43]2[C:49](Cl)=[O:50])[CH:39]=[CH:40][CH:41]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[F:35][C:36]1[CH:37]=[C:38]([CH:42]2[CH2:47][C:46](=[O:48])[CH2:45][CH2:44][N:43]2[C:49]([N:11]2[CH2:12][C:13]3[CH:18]=[C:17]([C:19]4[CH:20]=[C:21]5[N:27]([C:28]([O:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[O:29])[CH:26]=[N:25][C:22]5=[N:23][CH:24]=4)[CH:16]=[CH:15][C:14]=3[O:8][CH2:9][CH2:10]2)=[O:50])[CH:39]=[CH:40][CH:41]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 696753772-methylpropyl 6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate trifluoroacetic acid saltHCID 866720302-(3-Fluorophenyl)-4-oxopiperidine-1-carbonyl chloride

Product 1

HCID 708152472-methylpropyl 6-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-methylpropyl 6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate trifluoroacetic acid salt (0.20 g, 0.53 mmol), 2-(3-fluorophenyl)-4-oxopiperidine-1-carbonyl chloride (reagent preparation 37) (0.13 g, 0.51 mmol) and diisopropylethylamine (3.0 g, 23 mmol) in N,N-dimethylformamide (8 mL) was heated to 65° C. for 18 hours. The resulting mixture was diluted with ethyl acetate (50 mL) and washed with water (2×25 mL) and once with brine (15 mL) then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (acetone/ethyl acetate, 1:4) to give 2-methylpropyl 6-(4-{[2-(3-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate (0.19 g, 64% yield). MS (EI) for C35H35FN5O5: 586 (MH+)

Workup

  1. washwashed with water (2×25 mL) and once with brine (15 mL)
  2. dry with materialthen dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (acetone/ethyl acetate, 1:4)

Sources & evidence

ORD record
ord-3d402476621c4c4090c4608cf223e64f
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

Loading…