Diisopropylethylamine → 4-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241217

Reaction equation

HRID 241217 reaction equation
Cl.[CH3:2][C:3]1[N:4](C(OC(C)CC)=O)[C:5]2[C:6]([N:22]=1)=[N:7][CH:8]=[C:9]([C:11]1[CH:12]=[CH:13][C:14]3[O:20][CH2:19][CH2:18][NH:17][CH2:16][C:15]=3[CH:21]=1)[CH:10]=2.Cl[C:31]1[C:36]([CH3:37])=[C:35]([Cl:38])[N:34]=[CH:33][N:32]=1.C(N(C(C)C)CC)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[Cl:38][C:35]1[N:34]=[CH:33][N:32]=[C:31]([N:17]2[CH2:16][C:15]3[CH:21]=[C:11]([C:9]4[CH:10]=[C:5]5[NH:4][C:3]([CH3:2])=[N:22][C:6]5=[N:7][CH:8]=4)[CH:12]=[CH:13][C:14]=3[O:20][CH2:19][CH2:18]2)[C:36]=1[CH3:37]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 8188604,6-Dichloro-5-methylpyrimidineHCID 668205501-methylpropyl 2-methyl-6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate hydrochloride

Product 1

HCID 595865474-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepineYield 31%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 1-methylpropyl 2-methyl-6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate hydrochloride (0.213 g, 0.512 mmol, example 6, step 2), 4,6-dichloro-5-methylpyrimidine (0.100 g, 0.613 mmol), and diisopropylethylamine (0.330 g, 2.56 mmol) in N-methylpyrrolidinone (2 mL) was stirred at room temperature for 17 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with saturated sodium bicarbonate (50 mL) and brine (25 mL), and dried over sodium sulfate. Filtration, concentration and purification by column chromatography on silica (97:3 dichloromethane/methanol) provided 4-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (0.06 g, 31% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ 8.50 (s, 1H), 8.22 (s, 1H), 8.04 (s, 1H), 7.60 (s, 1H), 7.50 (d, 1H), 7.08 (d, 1H), 4.81 (s, 2H), 4.39-4.32 (m, 2H), 4.03-3.97 (m, 2H), 2.64 (s, 3H), 2.37 (s, 3H); MS (EI) for C21H19ClN6O: 407 (MH+).

Workup

  1. washwashed with saturated sodium bicarbonate (50 mL) and brine (25 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationFiltration, concentration and purification by column chromatography on silica (97:3 dichloromethane/methanol)

Sources & evidence

ORD record
ord-3651305455da4668bae59b235a2de84c
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Linked notes

Loading…