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 1666148ノート

反応式

HRID 1666148 の反応式
[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

参加物

5

反応物 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-ol2 回

生成物 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-carboxylate収率 40.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(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).

後処理

  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

出典と根拠

ORDレコード
ord-cfebd67426174f5e9f5d4b6e7714588e
出典データセット
uspto-grants-2011_10
特許番号
US08044043B2

反応ノート

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