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

HRID 473908Notes

Reaction equation

HRID 473908 reaction equation
[O:1]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[N:19]([C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]=[CH:21][N:22]=4)=[CH:14][CH:13]=3)=[CH:11][C:6]=2[CH2:5][NH:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[F:39][C:40]1[CH:45]=[CH:44][C:43]([CH:46]2[CH2:51][C:50](=[O:52])[CH2:49][CH2:48][N:47]2[C:53](Cl)=[O:54])=[CH:42][CH:41]=1>O1CCCC1.C(OCC)(=O)C>[F:39][C:40]1[CH:45]=[CH:44][C:43]([CH:46]2[CH2:51][C:50](=[O:52])[CH2:49][CH2:48][N:47]2[C:53]([N:4]2[CH2:5][C:6]3[CH:11]=[C:10]([C:12]4[CH:13]=[CH:14][C:15]([C:18]5[N:19]([C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]=[CH:21][N:22]=5)=[CH:16][CH:17]=4)[CH:9]=[CH:8][C:7]=3[O:1][CH2:2][CH2:3]2)=[O:54])=[CH:42][CH:41]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 67513954HCID 67513954, compoundHCID 866720332-(4-Fluorophenyl)-4-oxopiperidine-1-carbonyl chloride

Product 1

HCID 675151262-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylateYield 81.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution 2-methylpropyl 2-[4-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (0.22 g, 0.56 mmol) and diisopropylethylamine (0.50 mL, 2.81 mmol) in dimethylfomamide (10 mL) at 0° C. a solution of 2-(4-fluorophenyl)-4-oxopiperidine-1-carbonyl chloride (reagent preparation 37) (0.15 g, 0.59 mmol) in tetrahydrofuran (5 mL) was added and the reaction mixture was stirred for 2 hours at room temperature. The mixture was diluted with ethyl acetate (250 mL) and partitioned with water (100 mL). The organic layer was separated and washed with water (50 mL), 10% aqueous citric acid (50 mL), brine then dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (hexane-acetone 4:1 to 7:3) provided 2-methylpropyl 2-[4-(4-{[2-(4-fluorophenyl)-4-oxopiperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)phenyl]-1H-imidazole-1-carboxylate (0.28 g, 80%). 1H NMR (400 MHz, d6-DMSO): 7.73 (d, 1H), 7.68-7.61 (m, 4H), 7.62 (d, 1H), 7.54 (dd, 1H), 7.30 (m, 1H), 7.15 (d, 1H), 7.10 (m, 3H), 7.04 (d, 2H), 5.20 (t, 1H), 4.62 (s, 2H), 4.24 (m, 2H), 4.04 (d, 2H), 3.68 (m, 3H), 3.40 (m, 1H), 2.86 (m, 2H), 2.61 (m, 1H), 2.32 (2t, 1H), 1.86 (m, 1H), 0.76 (m, 6H). MS (EI) for C35H35FN4O5: 611 (MH+).

Workup

  1. custompartitioned with water (100 mL)
  2. customThe organic layer was separated
  3. washwashed with water (50 mL), 10% aqueous citric acid (50 mL), brine
  4. dry with materialthen dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-430c0bd3d8f04585acc8e46616e3b561
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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