Diisopropylethylamine → 6-{4-[(7S)-7-ethyl-5,6,7,8-tetrahydroquinazolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1H-imidazo[4,5-b]pyridin-2-amine

HRID 241236Notes

Reaction equation

HRID 241236 reaction equation
Cl.[O:2]1[C:8]2[CH:9]=[CH:10][C:11]([C:13]3[CH:14]=[C:15]4[NH:21][C:20]([NH:22]C(=O)OC)=[N:19][C:16]4=[N:17][CH:18]=3)=[CH:12][C:7]=2[CH2:6][NH:5][CH2:4][CH2:3]1.Cl[C:28]1[C:37]2[CH2:36][CH2:35][C@H:34]([CH2:38][CH3:39])[CH2:33][C:32]=2[N:31]=[CH:30][N:29]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.CO>[CH2:38]([C@@H:34]1[CH2:33][C:32]2[N:31]=[CH:30][N:29]=[C:28]([N:5]3[CH2:6][C:7]4[CH:12]=[C:11]([C:13]5[CH:14]=[C:15]6[NH:21][C:20]([NH2:22])=[N:19][C:16]6=[N:17][CH:18]=5)[CH:10]=[CH:9][C:8]=4[O:2][CH2:3][CH2:4]3)[C:37]=2[CH2:36][CH2:35]1)[CH3:39]

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 86647864(7S)-4-chloro-7-ethyl-5,6,7,8-tetrahydroquinazoline

Product 1

HCID 595861656-{4-[(7S)-7-ethyl-5,6,7,8-tetrahydroquinazolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1H-imidazo[4,5-b]pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of methyl [6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate hydrochloride (84 mg, 0.23 mmol, (7S)-4-chloro-7-ethyl-5,6,7,8-tetrahydroquinazoline (reagent preparation 3) (35 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.90 mmol) in N-methyl-2-pyrrolidone (2.0 mL) was reacted in a microwave apparatus (250 W) for 5 min. at 110° C. After cooling to room temperature the reaction mixture was diluted with methanol (2 mL) and purified by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile) to give 6-{4-[(7S)-7-ethyl-5,6,7,8-tetrahydroquinazolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1H-imidazo[4,5-b]pyridin-2-amine. 1H NMR (400 MHz, Methanol-d4): 8.33 (s, 1H), 8.13 (brs, 1H), 7.63 (s, 1H), 7.50 (brs, 1H), 7.31 (d, 1H), 7.04 (d, 1H), 4.75 (b, 2H), 4.44 (m, 1H), 4.24 (m, 1H), 3.99 to 3.86 (m, 2H), 2.94 to 2.86 (m, 2H), 2.60 (m, 1H), 2.28 (m, 1H), 1.97 (m, 1H), 1.75 (m, 1H), 1.36 (m, 2H), 1.14 (m, 1H), 0.97 (t, 3H); MS (EI) for C25H27N7O: 442 (MH+).

Workup

  1. customwas reacted in a microwave apparatus (250 W) for 5 min. at 110° C
  2. custompurified by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile)

Sources & evidence

ORD record
ord-2d3ba47b96754d77ad4a1c725df40331
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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