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

HRID 1687189Notes

Reaction equation

HRID 1687189 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.[CH3:21][C:22]1([CH3:34])[CH2:28][CH2:27][CH2:26][NH:25][C:24]2[CH:29]=[CH:30][C:31]([NH2:33])=[CH:32][C:23]1=2.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:33][C:31]2[CH:30]=[CH:29][C:24]3[NH:25][CH2:26][CH2:27][CH2:28][C:22]([CH3:34])([CH3:21])[C:23]=3[CH:32]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 672643035,5-Dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-amineHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264236N-{(1R,2R)-2-[5-Chloro-2-(5,5-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamideYield 17.2%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (112 mg, 0.330 mmol), 5,5-Dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamine (76 mg, 0.399 mmol), 4 N HCl in dioxane (99 ul) and 2-methoxyethanol (4 mL). Heated reaction to 120° C. for 24 hours. Concentrated under reduced pressure and purified with normal phase chromatography to yield a brown solid, N-{(1R,2R)-2-[5-Chloro-2-(5,5-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (28 mg, 17%). LCMS: m/z=493.30 (M+H+), 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.25 (m, 2H), 7.06 (br s, 1H), 6.68 (d, 1H, J=8.1 Hz), 5.76 (br s, 1H), 5.42 (m, 1H), 3.82 (m, 1H), 3.75 (m, 2H), 3.53 (m, 2H), 3.21 (m, 1H), 3.03 (m, 2H), 2.78 (s, 3H), 2.16 (m, 2H), 1.88 (m, 2H), 1.79 (m, 2H), 1.64 (m, 2H), 1.40 (m, 6H), 1.33 (m, 4H).

Workup

  1. temperatureHeated
  2. customreaction to 120° C. for 24 hours
  3. concentrationConcentrated under reduced pressure
  4. custompurified with normal phase chromatography

Sources & evidence

ORD record
ord-40acb22156b94eb0ad307ede8fdae6d7
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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