Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 67264567, compound

HRID 1041630Notes

Reaction equation

HRID 1041630 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]([CH2:20][CH3:21])[S:16]([CH3:19])(=[O:18])=[O:17])[C:5]([Cl:22])=[CH:4][N:3]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[NH2:38][C:39]1[CH:52]=[CH:51][C:42]2[NH:43][C:44](=[O:50])[CH2:45][CH2:46][C:47]([CH3:49])([CH3:48])[C:41]=2[CH:40]=1.C(=O)([O-])[O-]>C(O)(C)C>[Cl:22][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]([CH2:20][CH3:21])[S:16]([CH3:19])(=[O:18])=[O:17])=[N:7][C:2]([NH:38][C:39]2[CH:52]=[CH:51][C:42]3[NH:43][C:44](=[O:50])[CH2:45][CH2:46][C:47]([CH3:49])([CH3:48])[C:41]=3[CH:40]=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 578538307-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneHCID 86634062HCID 86634062, compound

Product 1

HCID 67264567HCID 67264567, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-N-ethyl-methanesulfonamide (99 mg, 0.27 mmol) in Isopropyl alcohol (4 mL) was added to 10-Camphorsulfonic acid (12 mg, 0.052 mmol) and 7-Amino-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (56 mg, 0.27 mmol) and was heated in a Microwave vial for 90 min 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 onto Celite. Chromatography (ISCO, 12 g silica gel, 40-80% EtOAc:Hex) afforded N-{(1R,2R)-2-[5-Chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-N-ethyl-methanesulfonamide as an off white foam (78 mg, 54%). LCMS: 535 (M+H); 1H-NMR, CDCl3: 7.91 (s, 1H), 7.74 (d, 1H, J=8.5 Hz), 7.34 (s, 1H), 7.25 (s, 1H), 7.00 (s, 1H), 6.88 (d, 1H J=8.5 Hz), 6.02 (d, 1H, J=8.2 Hz), 3.99 (m, 1H), 3.75 (m, 1H), 3.30 (m, 1H), 3.20 (m, 1H), 2.92 (s, 3H), 2.45 (m, 1H), 2.40 (t, 2H, J=7.0 Hz), 2.13 (t, 2H, J=7.0 Hz), 1.95 (m, 2H), 1.44 (s, 6H), 1.39 (m, 3H), 1.16 (t, 3H, J=7.0 Hz).

Workup

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

Sources & evidence

ORD record
ord-67279982bf174449b6bb5656dd792dca
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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