Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 25158498, compound

HRID 1687983Notes

Reaction equation

HRID 1687983 reaction equation
[NH2:1][C:2]1[C:12]2[O:11][CH2:10][CH2:9][NH:8][C:7](=[O:13])[C:6]=2[CH:5]=[C:4]([F:14])[CH:3]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.Cl[C:31]1[N:36]=[C:35]([NH:37][C@@H:38]2[CH2:43][CH2:42][CH2:41][CH2:40][C@H:39]2[NH:44][S:45]([CH3:48])(=[O:47])=[O:46])[C:34]([Cl:49])=[CH:33][N:32]=1.C(=O)([O-])[O-]>COCCO.C(Cl)Cl.CO>[Cl:49][C:34]1[C:35]([NH:37][C@@H:38]2[CH2:43][CH2:42][CH2:41][CH2:40][C@H:39]2[NH:44][S:45]([CH3:48])(=[O:47])=[O:46])=[N:36][C:31]([NH:1][C:2]2[C:12]3[O:11][CH2:10][CH2:9][NH:8][C:7](=[O:13])[C:6]=3[CH:5]=[C:4]([F:14])[CH:3]=2)=[N:32][CH:33]=1

Participants

7

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 67263491HCID 67263491, compoundHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 25158498HCID 25158498, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 80192-MethoxyethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

9-Amino-7-fluoro-3,4-dihydro-2H-benzo[f][1,4]oxazepin-5-one (59 mg, 0.30 mmol), 10-Camphorsulfonic acid (11 mg, 0.047 mmol) and N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (0.104 g, 0.306 mmol) in 2-Methoxyethanol (5 mL) were heated at 110° C. under an atmosphere of Nitrogen for 2 days. The mixture was cooled to r.t., neutralized with 100 mg MP-Carbonate and conc. in vacuo. The residue was partially taken up in DCM/MeOH, and the remainder was powdered onto Celite, then chromatographed (2×12 g silica gel, ISCO, 0-100% EtOAc:hexane, then 10% MeOH) to afford N-{(1R,2R)-2-[5-Chloro-2-(7-fluoro-5-oxo-2,3,4,5-tetrahydro-benzo[f][1,4]oxazepin-9-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a beige solid (69 mg, 46%). MP=177-181° C.; LCMS: 499 (M+H); 1H-NMR (CDCl3): 8.27 (dd, 1H, J=2.6, 10.9 Hz), 7.98 (1H, s), 7.62 (s, 1H), 7.03 (dd, 1H, J=2.9, 8.6 Hz), 6.95 (m, 1H), 6.85 (m, 1H), 6.02 (d, 1H, J=7.0 Hz), 4.21 (m, 1H), 4.15 (m, 1H), 3.82 (m, 1H), 3.32 (m, 3H), 2.98 (s, 3H), 2.33 (m, 1H), 2.18 (m, 1H), 1.87 (m, 1H), 1.78 (m, 1H), 1.64 (m, 1H), 1.41 (m, 2H), 1.22 (m, 1H).

Workup

  1. customchromatographed (2×12 g silica gel, ISCO, 0-100% EtOAc

Sources & evidence

ORD record
ord-925c17b6cdec4dc18a9751c5eae61aa3
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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