Hydrochloric Acid → 2-[5-Chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-piperidin-1-yl-benzamide

HRID 1040842Notes

Reaction equation

HRID 1040842 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:10]=2[C:11]([NH2:13])=[O:12])[C:5]([Cl:24])=[CH:4][N:3]=1.[NH2:25][C:26]1[CH:38]=[CH:37][C:29]2[N:30]([CH3:36])[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:28]=2[CH:27]=1.Cl>COC(O)C.O1CCOCC1>[Cl:24][C:5]1[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:10]=2[C:11]([NH2:13])=[O:12])=[N:7][C:2]([NH:25][C:26]2[CH:38]=[CH:37][C:29]3[N:30]([CH3:36])[C:31](=[O:35])[CH2:32][CH2:33][CH2:34][C:28]=3[CH:27]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 197602587-Amino-1-methyl-1,3,4,5-tetrahydro-benzo[B]azepin-2-oneHCID 866338852-(2,5-Dichloro-pyrimidin-4-ylamino)-5-piperidin-1-yl-benzamide

Product 1

HCID 668299562-[5-Chloro-2-(1-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-5-piperidin-1-yl-benzamideYield 21.1%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 30156371-MethoxyethanolSolvent

Conditions

Temperature
120 °C

Procedure

2-(2,5-dichloro-pyrimidin-4-ylamino)-5-piperidin-1-yl-benzamide (50.1 mg, 0.137 mmol) and 7-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (28.7 mg, 0.151 mmol) were slurried in methoxyethanol (2.0 mL) prior to adding ˜0.2 mL of 4N HCl in dioxane. This mixture was heated at 120° C. for 2 h. After quenching with saturated aqueous NaHCO3 solution (2 mL), the resulting precipitate was collected by filtration, successively washed water (5×2 mL) and ether (2×1 mL) to afford product (15 mg, 21%) as a yellow powder that had the following properties: mp: 295-297° C.; LC/MS (ESI+): 520 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 11.20 (s, 1H), 9.45 (s, 1H), 8.42 (d, J=8.0, 1H), 8.28 (s, 1H), 8.15 (s, 1H), 7.65 (m, 2H), 7.52 (d, J=8.9, 1H), 7.30 (s, 1H), 7.20 (d, J=8.6, 1H), 7.05 (d, J=9.4, 1H), 3.20 (s, 3H), 3.18 (m, 4H), 2.65-2.20 (series of m, 6H), 1.65 (m, 4H), 1.55 (m, 2H).

Workup

  1. customAfter quenching with saturated aqueous NaHCO3 solution (2 mL)
  2. filtrationthe resulting precipitate was collected by filtration, successively washed water (5×2 mL) and ether (2×1 mL)

Sources & evidence

ORD record
ord-dea069d8f4c84dc988f97eb11d805544
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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