Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 67263942, compound

HRID 1041633Notes

Reaction equation

HRID 1041633 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[N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[C:36]([O:37][CH3:38])=[CH:35][C:26]2[N:27]([CH2:33][CH3:34])[C:28](=[O:32])[CH2:29][CH2:30][CH2:31][C:25]=2[CH:24]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])[O-]>C(O)(C)C>[Cl:21][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])=[N:7][C:2]([NH:22][C:23]2[C:36]([O:37][CH3:38])=[CH:35][C:26]3[N:27]([CH2:33][CH3:34])[C:28](=[O:32])[CH2:29][CH2:30][CH2:31][C:25]=3[CH:24]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 672644367-Amino-1-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86634061HCID 86634061, compound

Product 1

HCID 67263942HCID 67263942, compoundYield 26.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-N-methyl-methanesulfonamide (79 mg, 0.22 mmol), 7-Amino-1-ethyl-8-methoxy-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (52 mg, 0.22 mmol), and 10-Camphorsulfonic acid (80 mg, 0.34 mmol) in Isopropyl alcohol (3 mL) and was heated in a microwave vial for 2 h at 120° C. Upon cooling, the mixture was treated with MP-Carbonate (2.69 mmol/g loading; 0.29 g, 0.78 mmol) for 1 h, was filtered and was concentrated in vacuo. Chromatography (ISCO, 2×12 g silica gel, 0-85% EtOAc:Hex) 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}-N-methyl-methanesulfonamide as a white foam (32 mg, 26%). LCMS: 551 (M+H), 1H-NMR (CDCl3): 8.20 (s, 1H), 7.93 (s, 1H), 7.44 (s, 1H), 6.70 (s, 1H), 5.61 (d, 1H, J=7.9 Hz), 4.11 (m, 2H), 3.90 (s, 3H), 3.78 (m, 1H), 2.84 (s, 3H), 2.75 (s, 3H), 2.59 (br s, 1H), 2.41 (m, 1H), 2.28 (m, 2H), 2.19 (br s, 1H), 1.90 (m, 3H), 1.71 (m, 1H), 1.2-1.5 (m, 6H), 1.14 (t, 3H, J=7.0 Hz).

Workup

  1. temperatureUpon cooling
  2. filtrationwas filtered
  3. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-63c110a2a7394088b03f7bf0f8cf89b1
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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