Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-5-chloro-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide

HRID 1041700Notes

Reaction equation

HRID 1041700 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]([C:11](=[O:13])[CH3:12])[CH2:7][CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])[O-]>C(O)(C)C>[C:11]([N:6]1[C:5]2[CH:14]=[CH:15][C:2]([NH:1][C:17]3[N:22]=[C:21]([NH:23][C:24]4[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:25]=4[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:35])=[CH:19][N:18]=3)=[CH:3][C:4]=2[O:10][CH2:9][CH2:8][CH2:7]1)(=[O:13])[CH3:12]

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 19660Carbonate IonHCID 672635641-(3-Amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanoneHCID 717421912-(2,5-Dichloropyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

Product 1

HCID 533213212-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-5-chloro-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

1-(3-Amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanone (97 mg, 0.47 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (169 mg, 0.536 mmol), and 10-Camphorsulfonic acid (16 mg, 0.070 mmol) in Isopropyl alcohol (4 mL) was irradiated in a CEM microwave (120° C., 30 min). The mixture was neutralized with MP-carbonate (0.3 mmol) and purified on silica gel (ISCO, 2×12 g, 0-100% EtOAc:Hex) to afford 2-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-5-chloro-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide as off white solids (122 mg, 53%). MP=226-228° C.; LCMS: 485 (M+H); 1H-NMR (DMSO): 9.51 (s, 1H), 9.42 (s, 1H), 9.56 (m, 1H), 8.21 (s, 1H), 7.49 (m, 2H), 7.42 (m, 1H), 7.36 (s, 1H), 7.17 (m, 1H), 7.05 (d, 1H, J=8.5 Hz), 4.54 (m, 1H), 4.32 (m, 1H), 3.55 (m, 1H), 2.74 (d, 3H, J=4.5 Hz), 1.92 (m, 1H), 1.71 (m, 4H), 1H obscured by solvent.

Workup

  1. custompurified on silica gel (ISCO, 2×12 g, 0-100% EtOAc:Hex)

Sources & evidence

ORD record
ord-79f45671acf543d0b1211242239adc70
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…