Sodium hydride → 1-(6-Chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyridin-3-yl-propan-2-ol

HRID 1469441노트

반응식

HRID 1469441 반응식
[Cl:1][C:2]1[C:10]2[NH:9][C:8]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:18][C:19]1([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH2:21][O:20]1>CN(C=O)C>[Cl:1][C:2]1[C:10]2[N:9]([CH2:18][C:19]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)([OH:20])[CH3:21])[C:8]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 50915806-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleHCID 230811803-(2-Methyloxiran-2-yl)pyridine

생성물 1

HCID 709847761-(6-Chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyridin-3-yl-propan-2-ol수율 38.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

6-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g, 4.5 mmol) was dissolved in 15 mL DMF and stirred for 5 min at RT. Sodium hydride (540 mg, 13.5 mmol) was added portionwise at RT under nitrogen. 3-(2-Methyl-oxiranyl)-pyridine (800 mg, 5.9 mmol) was diluted in 5 mL DMF and added dropwise at the same temperature and stirred for 16 h at RT. The reaction was monitored by TLC & LCMS. After consumption of starting material, the reaction mixture was quenched with ice water (30 mL) and filtered. The residue was crystallized in EtOH (1 mL) and ether (40 mL) and purified by reverse phase chromatography to obtain 620 mg of 1-(6-chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyridin-3-yl-propan-2-ol. 1H NMR (CDCl3, freebase) δ (ppm): 8.77 (s, 1H), 8.5 (d, 1H), 8.45 (s, 1H), 7.71 b (s, 1H), 7.17 b (s, 1H), 7.06 (d, 1H), 6.97 (t, 1H), 5.12 b (s, 1H), 4.3 b (s, 1H), 3.78 (m, 1H), 3.62 (m, 1H), 3.14 (m, 1H), 2.63 (m, 2H), 2.57 (s, 3H), 2.5 b (s, 2H), 1.53 (s, 3H). Separation by chiral HPLC provided enantiomers 57a and 57b.

후처리

  1. additionadded dropwise at the same temperature
  2. stirringstirred for 16 h at RT
  3. customAfter consumption of starting material
  4. customthe reaction mixture was quenched with ice water (30 mL)
  5. filtrationfiltered
  6. customThe residue was crystallized in EtOH (1 mL)
  7. customether (40 mL) and purified by reverse phase chromatography

출처 및 근거

ORD 기록
ord-d5a14ed6cb5949b5a834af61d87a0230
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006263B2

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