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

HRID 1041669Notes

Reaction equation

HRID 1041669 reaction equation
[CH2:1]([N:3]1[C:9]2[CH:10]=[C:11]([NH2:14])[CH:12]=[CH:13][C:8]=2[O:7][CH2:6][CH2:5][CH2:4]1)[CH3:2].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[CH3:30][NH:31][C:32]([C:34]1[S:35][CH:36]=[CH:37][C:38]=1[NH:39][C:40]1[C:45]([Cl:46])=[CH:44][N:43]=[C:42](Cl)[N:41]=1)=[O:33].C(=O)(O)[O-].[Na+]>C(O)(C)C.O>[CH3:30][NH:31][C:32]([C:34]1[S:35][CH:36]=[CH:37][C:38]=1[NH:39][C:40]1[C:45]([Cl:46])=[CH:44][N:43]=[C:42]([NH:14][C:11]2[CH:12]=[CH:13][C:8]3[O:7][CH2:6][CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[C:9]=3[CH:10]=2)[N:41]=1)=[O:33]

Participants

7

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 672640079-Ethyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamineHCID 866340043-(2,5-Dichloro-pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methylamide

Product 1

HCID 668296613-[5-Chloro-2-(9-ethyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamideYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

9-Ethyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamine (57 mg, 0.30 mmol), 10-Camphorsulfonic acid (72.3 mg, 0.311 mmol) and 3-(2,5-Dichloro-pyrimidin-4-ylamino)-thiophene-2-carboxylic acid methylamide (9.0E1 mg, 0.30 mmol) in Isopropyl alcohol (2.0 mL) was irradiated in a CEM microwave (120° C., 30 min). The mixture was diluted with satd. sodium bicarbonate (1 mL) and water (6 mL). The flocculent solids were separated from an oily residue on the sides of the vial, filtered and washed with water. Drying in vacuo of the solids furnished 3-[5-Chloro-2-(9-ethyl-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-thiophene-2-carboxylic acid methylamide (67 mg, 49%). MP=153-155° C.; LCMS: 459 (M+H); 1H-NMR (CDCl3): 11.27 (s, 1H), 8.31 (d, 1H, J=5.1 Hz), 8.08 (s, 1H), 6.92 (s, 1H), 6.88 (m, 2H), 6.71 (s, 1H), 5.67 (s, 1H), 4.14 (m, 2H), 3.29 (m, 2H), 3.27 (m, 2H), 3.02 (d, 3H, J=4.8 Hz), 2.03 (m, 2H), 1.18 (t, 3H, J=6.4 Hz).

Workup

  1. additionThe mixture was diluted with satd
  2. customThe flocculent solids were separated from an oily residue on the sides of the vial,
  3. filtrationfiltered
  4. washwashed with water
  5. customDrying in vacuo of the solids

Sources & evidence

ORD record
ord-9ae2f66278d945c990138412d0e3a4fb
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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