Hydrochloric Acid → N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

HRID 1687183Notes

Reaction equation

HRID 1687183 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:37]=[CH:36][C:25]2[N:26]([CH2:34][CH3:35])[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@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[N:7][C:2]([NH:21][C:22]2[CH:37]=[CH:36][C:25]3[N:26]([CH2:34][CH3:35])[C:27](=[O:33])[CH2:28][CH2:29][C:30]([CH3:31])([CH3:32])[C:24]=3[CH:23]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 672637817-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264104N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamideYield 38.4%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (114 mg, 0.336 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (80 mg, 0.344 mmol), 4 N HCl in dioxane (103 ul) and 2-methoxyethanol (5 mL). Heated reaction to 120° C. for 2.5 hours. Evaporated off solvent and purified with normal phase chromatography to yield a white solid, N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (69 mg, 38%). LCMS: m/z=535.34 (M+H+), 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.65 (dd, 1H, J=8.6, 1.3 Hz), 7.36 (d, 1H, J=2.3 Hz), 7.21 (d, 1H, J=8.6 Hz), 6.91 (s, 1H), 5.44 (d, 1H, J=7.6 Hz), 5.36 (d, 1H, J=6.8 Hz), 3.87 (m, 3H), 3.24 (m, 1H), 2.82 (s, 3H), 2.17 (m, 6H), 1.84 (m, 2H), 1.37 (m, 13H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 2.5 hours
  3. customEvaporated off solvent
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-f4325ca8f45b487f9a85a6efa97f90e1
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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