Diisopropylethylamine → methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate

HRID 473887Notes

Reaction equation

HRID 473887 reaction equation
[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9](Cl)=[O:10])[CH2:5][CH2:4]1.Cl.[O:13]1[C:19]2[CH:20]=[CH:21][C:22]([C:24]3[CH:25]=[C:26]4[NH:32][C:31]([NH:33][C:34](=[O:37])[O:35][CH3:36])=[N:30][C:27]4=[N:28][CH:29]=3)=[CH:23][C:18]=2[CH2:17][NH:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O>[F:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([N:16]2[CH2:17][C:18]3[CH:23]=[C:22]([C:24]4[CH:25]=[C:26]5[NH:32][C:31]([NH:33][C:34](=[O:37])[O:35][CH3:36])=[N:30][C:27]5=[N:28][CH:29]=4)[CH:21]=[CH:20][C:19]=3[O:13][CH2:14][CH2:15]2)=[O:10])[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 86647862methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate hydrochlorideHCID 866720264-(Fluoromethyl)piperidine-1-carbonyl chloride

Product 1

HCID 49833673methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamateYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(fluoromethyl)piperidine-1-carbonyl chloride (reagent preparation 37) (24 mg, 0.13 mmol), methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate hydrochloride (34 mg, 0.091 mmol), and diisoproylethylamine (59 mg, 0.45 mmol) in dichloromethane (0.5 mL) and N,N-dimethylformamide (0.5 mL) was stirred at room temperature for one hour. The reaction mixture was concentrated then dissolved in methanol (2 mL) and purified directly by preparative reverse phase HPLC to give methyl [6-(4-{[4-(fluoromethyl)piperidin-1-yl]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate, (21 mg, 48% yield), (400 MHz, DMSO-d6): 8.41 (br, 1H), 7.87 (s, 1H), 7.54 to 7.44 (m, 2H), 7.05 (d, 1H), 4.45 (s, 2H), 4.31 (dd, 2H), 4.19 (m, 2H), 3.67 to 3.55 (m, 4H), 2.74 (t, 2H), 1.84 (br, 1H), 1.67 to 1.58 (m, 2H), 1.29 to 1.18 (m, 2H); MS (EI) for C24H27FN6O4: 483 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthen dissolved in methanol (2 mL)
  3. custompurified directly by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-c8da5f3da6814b59afcd00e8584206ea
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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