Hydrochloric Acid → 7-{5-Chloro-4-[2-(1-methyl-1H-imidazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one

HRID 1687193Notes

Reaction equation

HRID 1687193 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=2)[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:36]=[CH:35][C:26]2[NH:27][C:28](=[O:34])[CH2:29][CH2:30][C:31]([CH3:33])([CH3:32])[C:25]=2[CH:24]=1.Cl>O1CCOCC1.COCCO>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[N:16]([CH3:20])[CH:17]=[CH:18][N:19]=2)=[N:7][C:2]([NH:22][C:23]2[CH:36]=[CH:35][C:26]3[NH:27][C:28](=[O:34])[CH2:29][CH2:30][C:31]([CH3:33])([CH3:32])[C:25]=3[CH:24]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 578538307-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86633891(2,5-Dichloro-pyrimidin-4-yl)-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-amine

Product 1

HCID 510310027-{5-Chloro-4-[2-(1-methyl-1H-imidazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneYield 82.5%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined (2,5-Dichloro-pyrimidin-4-yl)-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-amine (82 mg, 0.256 mmol), 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (63 mg, 0.308 mmol), 4 N HCl in dioxane (80 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 6 hours. Evaporated off solvent and purified with normal phase chromatography to yield a light brown solid, 7-{5-Chloro-4-[2-(1-methyl-1H-imidazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (103 mg, 82%). mp 227° C.; LCMS: m/z=488.23 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.20 (m, 1H), 7.95 (s, 1H), 7.54 (dd, 1H, J=8.5, 2.4 Hz), 7.39 (m, 4H), 7.24 (m, 2H), 7.01 (d, 1H, J=1.3 Hz), 6.81 (d, 1H, J=8.6 Hz), 6.71 (m, 1H), 6.53 (dd, 1H, J=8.2, 2.7 Hz), 3.67 (s, 3H), 2.30 (m, 2H), 2.03 (m, 2H), 1.29 (s, 6H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 6 hours
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-d7e55d9182ba43028e61dec62d289440
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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