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

HRID 1041697Notes

Reaction equation

HRID 1041697 reaction equation
[CH:1]1[C:6]2[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:5]=2[CH:4]=[C:3]([NH2:12])[CH:2]=1.Cl[C:14]1[N:19]=[C:18]([NH:20][C:21]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:22]=2[C:23]([NH:25][CH3:26])=[O:24])[C:17]([Cl:32])=[CH:16][N:15]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(O)(C)C>[Cl:32][C:17]1[C:18]([NH:20][C:21]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:22]=2[C:23]([NH:25][CH3:26])=[O:24])=[N:19][C:14]([NH:12][C:3]2[CH:2]=[CH:1][C:6]3[NH:7][CH2:8][CH2:9][CH2:10][O:11][C:5]=3[CH:4]=2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 672637576,7,8,9-Tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamineHCID 717421912-(2,5-Dichloropyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

Product 1

HCID 508983482-[5-Chloro-2-(6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamideYield 9.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

6,7,8,9-Tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamine (0.115 g, 0.700 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (0.243 g, 0.770 mmol), and 10-Camphorsulfonic acid (251 mg, 1.08 mmol) in Isopropyl alcohol (4.00 mL) was irradiated in a CEM microwave (120° C., 30 min). The mixture was filtered and purified directly by HPLC to give enriched product, which was conc. and repurified. The fractions were concentrated and neutralized with MP-carbonate resin to afford 2-[5-Chloro-2-(6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-3-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide as a yellow foam (29 mg, 9%). LCMS: 443; 1H-NMR (CDCl3): 8.65 (s, 1H), 8.04 (m, 2H), 7.45 (m, 1H), 7.30 (m, 3H), 7.12 (s, 1H), 6.82 (m, 1H), 6.69 (m, 1H), 6.55 (d, 1H, J=8.4 Hz), 6.10 (q, 1H, J=4.0 Hz), 4.00 (t, 2H, J=5.2 Hz), 3.15 (t, 2H, J=5.5 Hz), 2.91 (d, 3H, J=4.8 Hz), 1.98 (m, 2H).

Workup

  1. filtrationThe mixture was filtered
  2. custompurified directly by HPLC
  3. customto give enriched product, which
  4. customrepurified
  5. concentrationThe fractions were concentrated

Sources & evidence

ORD record
ord-ecbe0b41e642432f931478270bd63b6f
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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