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

HRID 1687194Notes

Reaction equation

HRID 1687194 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[N:15]2[CH:19]=[CH:18][CH:17]=[N:16]2)[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:35]=[CH:34][C:25]2[NH:26][C:27](=[O:33])[CH2:28][CH2:29][C:30]([CH3:32])([CH3:31])[C:24]=2[CH:23]=1.Cl>O1CCOCC1.COCCO>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:15]2[CH:19]=[CH:18][CH:17]=[N:16]2)=[N:7][C:2]([NH:21][C:22]2[CH:35]=[CH:34][C:25]3[NH:26][C:27](=[O:33])[CH2:28][CH2:29][C:30]([CH3:32])([CH3:31])[C:24]=3[CH:23]=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 57853883(2,5-Dichloro-pyrimidin-4-yl)-(2-pyrazol-1-yl-phenyl)-amine

Product 1

HCID 668302907-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneYield 82%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined (2,5-Dichloro-pyrimidin-4-yl)-(2-pyrazol-1-yl-phenyl)-amine (82 mg, 0.268 mmol), 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (70 mg, 0.343 mmol), 4 N HCl in dioxane (80 ul) and 2-methoxyethanol (4 mL). Heated reaction at 120° C. for 16 hours. Evaporated off solvent and purified with normal phase chromatography to yield a beige solid, 7-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (104 mg, 82%). LCMS: m/z=474.34 (M+H+), 1H NMR (400 MHz, CD3OD) δ 8.41 (d, 1H, J=8.1 Hz), 8.02 (m, 2H), 7.84 (s, 1H), 7.60 (dd, 1H, J=8.3, 2.3 Hz), 7.52 (m, 2H), 7.42 (m, 1H), 7.30 (m, 1H), 6.91 (d, 1H, J=8.6 Hz), 6.55 (m, 1H), 4.59 (s, 1H), 2.32 (m, 2H), 2.11 (m, 2H), 1.35 (s, 6H).

Workup

  1. temperatureHeated
  2. customreaction at 120° C. for 16 hours
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-50942b98344647eca335f1dd2a1eb253
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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