Sodium hydride → (6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate

HRID 1666148노트

반응식

HRID 1666148 반응식
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:22][CH2:21][C@@H:20]([OH:23])[C:12]2=[N:13][CH:14]=[C:15]([N:17]([CH3:19])[CH3:18])[CH:16]=[C:11]2[CH2:10]1.[H-].[Na+].[O:26]=[C:27]1[NH:35][C:30]2=[N:31][CH:32]=[CH:33][CH:34]=[C:29]2[N:28]1[CH:36]1[CH2:41][CH2:40][N:39]([C:42](OC2C=CC([N+]([O-])=O)=CC=2)=[O:43])[CH2:38][CH2:37]1>C1COCC1>[O:26]=[C:27]1[NH:35][C:30]2=[N:31][CH:32]=[CH:33][CH:34]=[C:29]2[N:28]1[CH:36]1[CH2:37][CH2:38][N:39]([C:42]([O:23][C@H:20]2[C:12]3=[N:13][CH:14]=[C:15]([N:17]([CH3:19])[CH3:18])[CH:16]=[C:11]3[CH2:10][C@H:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])[CH2:22][CH2:21]2)=[O:43])[CH2:40][CH2:41]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 579114044-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylateHCID 57911469(6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol2회

생성물 1

HCID 57911425(6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate수율 40.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

(6R,9R)-6-(2,3-Difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (27.6 mg, 0.087 mmol) with stirring bar was azeotroped by benzene. Sodium hydride (20.80 mg, 0.867 mmol) was added to the THF (3 mL) suspension of (6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (27.6 mg, 0.087 mmol) and 4-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (43.2 mg, 0.113 mmol) at rt. The reaction was stirred at this temperature overnight. The reaction was quenched by water and partitioned between ethyl acetate and water. The ethyl acetate layer was washed by water two more times before dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 4% to 8% gave the desired product (19.8 mg, 36%). MS(ESI)[M+H−]=563.35; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 10.30 (br.s., 1H) 8.08 (d, J=5.49 Hz, 1H) 7.95-8.05 (m, 1H) 7.37-7.53 (m, 1H) 6.94-7.14 (m, 4H) 6.79 (br.s., 1H) 6.00 (d, J=10.38 Hz, 1H) 4.66 (br.m., 3H) 3.32 (t, J=12.67 Hz, 1H) 3.08 (br.m., 2H) 2.91-3.02 (m, 6H) 2.29 (d, J=13.73 Hz, 2H) 2.13-2.24 (m, 2H) 1.86-2.07 (m, 2H) 1.20-1.40 (m, 3H) 0.75-0.98 (m, 1H).

후처리

  1. customwas azeotroped by benzene
  2. customThe reaction was quenched by water
  3. custompartitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed by water two more times
  5. dry with materialbefore dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-cfebd67426174f5e9f5d4b6e7714588e
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044043B2

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