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-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1041677Notes

Reaction equation

HRID 1041677 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][CH2:10][CH2:9][CH2:8][N:7]([C:12](=[O:14])[CH3:13])[C:6]=2[CH:15]=1.Cl[C:17]1[N:22]=[C:21]([NH:23][C:24]2[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:34])=[CH:19][N:18]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)(O)[O-].[Na+].ClC1N=CC=CN=1>C(O)(C)C.O>[C:12]([N:7]1[C:6]2[CH:15]=[C:2]([NH:1][C:17]3[N:22]=[C:21]([NH:23][C:24]4[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=4[C:26]([NH:28][CH3:29])=[O:27])[C:20]([Cl:34])=[CH:19][N:18]=3)[CH:3]=[CH:4][C:5]=2[O:11][CH2:10][CH2:9][CH2:8]1)(=[O:14])[CH3:13]

Participants

8

Reactant 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 744042-ChloropyrimidineHCID 516892Sodium BicarbonateHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 672643681-(2-amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanone

Product 1

HCID 668296632-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamideYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

1-(2-Amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanone (55 mg, 0.27 mmol), 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (85 mg, 0.29 mmol), and 10-Camphorsulfonic acid (12 mg, 0.052 mmol) in Isopropyl alcohol (2 mL) was irradiated in a CEM microwave (120° C., 40 min). The contents were neutralized with 1 mL satd. sodium bicarbonate and diluted with 4 mL water to afford a turbid solution. This solution was added to stirring water (10 mL) resulting in ppt of the target and the chloropyrimidine traces. The solid was chromatographed (SiO2, 0-100% EtOAc:Hex) to afford 2-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide as a light yellow foam (54 mg, 43%). LCMS: 467 (M+H); 1H-NMR (DMSO): 11.51 (s, 1H), 9.50 (s, 1H), 8.75 (s, 1H), 8.64 (s, 1H), 8.24 (s, 1H), 7.73 (m, 2H), 7.45 (m, 2H), 7.14 (m, 1H), 7.03 (d, 1H, J=8.8 Hz), 4.60 (m, 1H), 4.30 (m, 1H), 3.62 (m, 1H), 2.91 (d, 1H, J=4 Hz), 2.77 (m, 1H), 1.93 (m, 1H), 1.74 (m, 4H).

Workup

  1. customto afford a turbid solution
  2. additionThis solution was added
  3. customresulting in ppt of the target
  4. customThe solid was chromatographed (SiO2, 0-100% EtOAc:Hex)

Sources & evidence

ORD record
ord-fec30c5686c243c59cad6e5529849ce4
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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