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

HRID 1041676Notes

Reaction equation

HRID 1041676 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.CN[C:18]([C:20]1[S:21][CH:22]=[CH:23][C:24]=1[NH:25][C:26]1[C:31]([Cl:32])=[CH:30][N:29]=[C:28](Cl)[N:27]=1)=[O:19].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=[O:36]>C(O)(C)C.CS(C)=O>[C:12]([N:7]1[C:6]2[CH:15]=[C:2]([NH:1][C:28]3[N:27]=[C:26]([NH:25][C:24]4[CH:23]=[CH:22][S:21][C:20]=4[C:18]([OH:19])=[O:36])[C:31]([Cl:32])=[CH:30][N:29]=3)[CH:3]=[CH:4][C:5]=2[O:11][CH2:10][CH2:9][CH2:8]1)(=[O:14])[CH3:13]

Participants

6

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 672643681-(2-amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanoneHCID 866340043-(2,5-Dichloro-pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methylamide

Product 1

HCID 672641673-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent

Procedure

1-(2-Amino-7,8-dihydro-6H-5-oxa-9-aza-benzocyclohepten-9-yl)-ethanone (55 mg, 0.27 mmol), 3-(2,5-Dichloro-pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methylamide (88 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; 140° C. 20 min, 140° C. 60 min, 140° C. 20 min). The mixture was conc. in vacuo and suspended in DMSO (3.5 mL), which resulted in a significant amount of solid to form. The solids were triturated in hexane:EtOAc, washed with hexane and dried in vacuo to give 3-[2-(9-Acetyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamideas an off white solid (45 mg, 36%). MP>260° C.; LCMS: 473 (M+H); 1H-NMR (DMSO): 11.64 (s, 1H), 9.56 (s, 1H), 8.43 (s, 1H), 8.26 (m, 2H), 7.75 (d, 1H, J=4 Hz), 7.70 (s, 1H), 7.48 (d, 1H, J=7.1 Hz), 7.07 (d, 1H, J=8.4 Hz), 4.60 (m, 1H), 4.32 (m, 1H), 3.64 (m, 1H), 2.77 (m, 4H), 1.97 (m, 1H), 1.80 (m, 4H).

Workup

  1. customwhich resulted in a significant amount of solid
  2. customto form
  3. customThe solids were triturated in hexane
  4. washEtOAc, washed with hexane
  5. customdried in vacuo

Sources & evidence

ORD record
ord-60eb73d0ef98409192836aa55f6f133f
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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