Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 67264423, compound

HRID 1687990Notes

Reaction equation

HRID 1687990 reaction equation
C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[CH2:16]([N:18]1[C:24]2[CH:25]=[C:26]([F:30])[C:27]([NH2:29])=[CH:28][C:23]=2[O:22][CH2:21][CH2:20][CH2:19]1)[CH3:17].Cl[C:32]1[N:37]=[C:36]([NH:38][C@@H:39]2[CH2:44][CH2:43][CH2:42][CH2:41][C@H:40]2[NH:45][S:46]([CH3:49])(=[O:48])=[O:47])[C:35]([Cl:50])=[CH:34][N:33]=1.C(=O)([O-])[O-]>C(O)(C)C.C(Cl)Cl>[Cl:50][C:35]1[C:36]([NH:38][C@@H:39]2[CH2:44][CH2:43][CH2:42][CH2:41][C@H:40]2[NH:45][S:46]([CH3:49])(=[O:48])=[O:47])=[N:37][C:32]([NH:29][C:27]2[C:26]([F:30])=[CH:25][C:24]3[N:18]([CH2:16][CH3:17])[CH2:19][CH2:20][CH2:21][O:22][C:23]=3[CH:28]=2)=[N:33][CH:34]=1

Participants

7

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 672638939-Ethyl-2-fluoro-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamineHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264423HCID 67264423, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

10-Camphorsulfonic acid (70 mg, 0.30 mmol) was added to 9-Ethyl-2-fluoro-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamine (58 mg, 0.28 mmol) and N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (94 mg, 0.28 mmol) in Isopropyl alcohol (1 mL). The mixture was irradiated in a CEM microwave (140° C., min). MP-Carbonate (2.69 mmol/g loading; 0.22 g, 0.5793156293 mmol) and DCM (2 mL) were added and the mixture stirred for 1 h, then filtered onto a 5 g SiO2 cartridge, which was air dried. The sample was chromatographed (ISCO, 2×12 g SiO2, 0-50% EtOAc:Hex) to afford N-{(1R,2R)-2-[5-Chloro-2-(9-ethyl-2-fluoro-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a purple film (40 mg, 30%). LCMS 513 (M+H), 1H-NMR (CDCl3): 7.92 (s, 1H), 7.76 (d, 1H, J=8.4 Hz), 6.76 (s, 1H), 6.62 (d, 1H, J=13.3 Hz), 5.39 (d, 1H, J=7.4 Hz), 5.11 (d, 1H, J=7.1 Hz), 4.09 (t, 2H, J=6.0 Hz), 3.93 (m, 1H), 3.25 (m, 5H), 2.81 (s, 3H), 2.20 (m, 2H), 2.00 (m, 2H), 1.82 (m, 2H), 1.43 (m, 4H), 1.20 (t, 3H, J=7.0 Hz). 19F-NMR: −135.

Workup

  1. customThe mixture was irradiated in a CEM microwave (140° C., min)
  2. filtrationfiltered onto a 5 g SiO2 cartridge, which
  3. customdried
  4. customThe sample was chromatographed (ISCO, 2×12 g SiO2, 0-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-861ddad704f242b2b4477943fc9eb901
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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