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 1688011노트

반응식

HRID 1688011 반응식
[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]

참가 물질

7

반응물 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

생성물 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 methylamide수율 49%

시약·촉매·용매 2

HCID 962Water용매HCID 3776Isopropanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1f3747c35e4547ce81116f13ea8e27e1
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148391B2

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