4-(Oxiran-2-yl)pyridine → 2-(9-Methyl-1,2,3,4,5,10c-hexahydro-3a,6,7-triaza-cyclopenta[c]fluoren-6-yl)-1-pyridin-4-yl-ethanol

HRID 1630651ノート

反応式

HRID 1630651 の反応式
[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[NH:11][C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1.CC(C)([O-])C.[K+].[O:24]1[CH2:26][CH:25]1[C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1>CN(C=O)C>[CH3:1][C:2]1[CH:14]=[N:13][C:12]2[N:11]([CH2:26][CH:25]([C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[OH:24])[C:10]3[CH2:9][CH2:8][N:7]4[CH2:15][CH2:16][CH2:17][CH:6]4[C:5]=3[C:4]=2[CH:3]=1

参加物

5

反応物 3

HCID 109534834-(Oxiran-2-yl)pyridineHCID 23665647Potassium tert-butoxideHCID 674346819-methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene

生成物 1

HCID 682833892-(9-Methyl-1,2,3,4,5,10c-hexahydro-3a,6,7-triaza-cyclopenta[c]fluoren-6-yl)-1-pyridin-4-yl-ethanol収率 43.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

9-Methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6,7-triaza-cyclopenta[c]fluorene (600 mg, 2.643 mmol) was dissolved in DMF (18 mL), and cooled to 0° C. Potassium tert-butoxide (444 mg, 3.964 mmol) was added and stirred for 5 min. 4-Oxiranyl-pyridine (639 mg, 5.286 mmol) in DMF (3 mL) was added dropwise into the reaction mixture and the mixture was stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After consumption of starting material, the reaction mixture was quenched with ice cold water (100 mL) and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (4×70 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by reverse phase chromatography to obtain 400 mg of 2-(9-Methyl-1,2,3,4,5,10c-hexahydro-3a,6,7-triaza-cyclopenta[c]fluoren-6-yl)-1-pyridin-4-yl-ethanol. 1H NMR (CD3OD, HCl salt) δ (ppm): 8.8 (d, 2H), 8.2 (d, 2H), 8.1 (s, 1H), 7.9 (s, 1H), 5.38 (m, 1H), 5.09 (t, 1H), 4.68 (dd, 2H), 4.4 (m, 1H), 3.75 (m, 4H), 3.43 (m, 2H), 2.7 (m, 2H), 2.46 (s, 3H), 2.2 (m, 3H). Separation by chiral HPLC provided diastereomers IV-209a-d.

後処理

  1. stirringthe mixture was stirred at RT for 12 h
  2. customAfter consumption of starting material
  3. customthe reaction mixture was quenched with ice cold water (100 mL)
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layer was washed with water (4×70 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto obtain the crude product, which
  9. customwas purified by reverse phase chromatography

出典と根拠

ORDレコード
ord-c605161ee02e4093aa83241b2e44d757
出典データセット
uspto-grants-2014_07
特許番号
US08791132B2

反応ノート

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