Hydrochloric Acid → N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

HRID 1040657Notes

Reaction equation

HRID 1040657 reaction equation
[NH2:1][C:2]1[C:15]([O:16][CH3:17])=[CH:14][C:5]2[N:6]([CH2:12][CH3:13])[C:7](=[O:11])[CH2:8][CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl[C:19]1[N:24]=[C:23]([NH:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]2[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:22]([Cl:37])=[CH:21][N:20]=1.Cl.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>O1CCOCC1>[Cl:37][C:22]1[C:23]([NH:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]2[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])=[N:24][C:19]([NH:1][C:2]2[C:15]([O:16][CH3:17])=[CH:14][C:5]3[N:6]([CH2:12][CH3:13])[C:7](=[O:11])[CH2:8][CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 672644367-Amino-1-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264125N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combined 7-Amino-1-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (124.8 mg, 0.0005327 mol), N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (180 mg, 0.00053 mol), 4 M of Hydrogen chloride in 1,4-Dioxane (200 uL) and heat in a Radley tube for 4.5 h at 110° C. Cool to RT and then treated with xs solid MP-carbonate resin and stirred for 30 min. Filtration, followed by concentration afforded a gummy solid that was put on high-vac overnight. The mixture was purified by ISCO chromoatography (40 g SiO2, 30% EA/hexane to 100% EA) afforded N-{(1R,2R)-2-[5-Chloro-2-(1-ethyl-8-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as an off-white foam that was dried under high vac and broken into a powder (112.41 mg, 39%). MP: 120-128° C. 1H-NMR (DMSO, 400 MHz) δ 8.10 (s, 1H), 7.96 (d, J=1.1 Hz, 1H), 7.69 (s, 1H), 7.18 (d, J=8.3 Hz, 1H), 7.00 (s, 1H), 6.85 (d, J=7.9 Hz, 1H), 3.88-3.83 (m, 1H), 3.35-3.31 (m, 1H), 2.90 (s, 3H), 2.60 (broad s, 2H), 2.11-2.00 (m, 8H), 1.70-1.67 (m, 2H), 1.40-1.15 (m, 5H), 1.00 (t, J=6.9 Hz, 3H); LC/MS: 537.34 (M+H).

Workup

  1. filtrationFiltration
  2. concentrationfollowed by concentration
  3. customafforded a gummy solid
  4. waitthat was put on high-vac overnight
  5. customThe mixture was purified by ISCO chromoatography (40 g SiO2, 30% EA/hexane to 100% EA)

Sources & evidence

ORD record
ord-bdf41fc528254046811ab6a2f34a2307
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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