Sodium hydride → 2-(pyridin-3-yl)-1-(2,8,9-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-ol

HRID 1469559ノート

反応式

HRID 1469559 の反応式
[CH3:1][N:2]1[CH2:16][CH2:15][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:14])=[C:11]([CH3:13])[C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[CH3:19][C:20]1([C:23]2[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=2)[CH2:22][O:21]1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([C:20]([OH:21])([CH3:22])[CH2:19][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:14])=[C:11]([CH3:13])[C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:16][CH2:15][C:5]2=3)[CH:24]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 230811803-(2-Methyloxiran-2-yl)pyridineHCID 682843422,8,9-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

生成物 1

HCID 682832292-(pyridin-3-yl)-1-(2,8,9-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-ol収率 61.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

2,8,9-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (400 mg, 1.86 mmol) 4 mL DMF, cooled to 0° C. and sodium hydride (224 mg, 5.60 mmol) was added portionwise at the same temperature. 3-(2-methyloxiran-2-yl)pyridine (504 mg, 3.73 mmol) in DMF (1 mL) was added to the reaction mixture and allowed to stir at RT for 12 h. After complete consumption of starting material, the reaction mixture was poured in to ice water and extracted with EtOAc (3×100 mL). The combined organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was crystallized with ether and hexane to obtain 400 mg of 2-(pyridin-3-yl)-1-(2,8,9-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-ol. 1H NMR (DMSO, freebase) δ (ppm): 8.59 (s, 1H), 8.42 (d, 1H), 7.73 (d, 1H), 7.31 (t, 1H), 7.1 (d, 1H), 6.73 (d, 1H), 4.11 (dd, 2H), 3.74 (s, 2H), 3.4 (m, 2H), 2.6 (m, 2H), 2.37 (s, 6H), 2.22 (s, 3H), 1.5 (s, 3H). Separation by chiral HPLC provides enantiomers II-145a-b.

後処理

  1. customAfter complete consumption of starting material
  2. additionthe reaction mixture was poured in to ice water
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic layer was washed with water (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto obtain the crude product, which
  8. customwas crystallized with ether and hexane

出典と根拠

ORDレコード
ord-335bdbf96e404ab1b2e2b8e6ca711359
出典データセット
uspto-grants-2015_04
特許番号
US09006263B2

反応ノート

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