Sodium hydride → 1-Pyridin-4-yl-2-(6,8,8-trimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-ethanol

HRID 1630488노트

반응식

HRID 1630488 반응식
[CH3:1][N:2]1[CH2:14][C:13]([CH3:16])([CH3:15])[C:12]2[NH:11][C:10]3[N:9]=[CH:8][CH:7]=[CH:6][C:5]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:19]1[CH2:21][CH:20]1[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][C:22]([CH:20]([OH:19])[CH2:21][N:11]2[C:10]3[N:9]=[CH:8][CH:7]=[CH:6][C:5]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:14][C:13]([CH3:16])([CH3:15])[C:12]2=3)=[CH:23][CH:24]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 682837476,8,8-Trimethyl-6,7,8,9-tetrahydro-5H-1,6,9-triaza-fluorene

생성물 1

HCID 682838921-Pyridin-4-yl-2-(6,8,8-trimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-ethanol수율 9.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

6,8,8-Trimethyl-6,7,8,9-tetrahydro-5H-1,6,9-triaza-fluorene (100 mg, 0.465 mmol) was dissolved in DMF (2 mL) and sodium hydride (56 mg, 1.39 mmol) was added portionwise under nitrogen. 4-Oxiranyl-pyridine (113 mg, 0.933 mmol) was added dropwise at RT and stirred for 12 h. After consumption of starting material (by monitoring TLC and LCMS), the reaction mixture was poured in to ice water and extracted with EtOAc (2×25 mL). The combined organic layer was washed with water (5×10 mL), the organic layer was dried over anhydrous sodium sulfate and concentrated, and the crude product purified by reverse phase chromatography to obtain 15 mg of 1-pyridin-4-yl-2-(6,8,8-trimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-ethanol. 1HNMR (CDCl3, freebase) δ (ppm): 8.63 (d, 2H), 8.22 (d, 1H), 7.75 (d, 1H), 7.45 (d, 2H), 7.09 (dd, 1H), 5.17 (d, 1H), 4.53 (dd, 1H), 4.47 (d, 1H), 3.71 (d, 1H), 3.44 (d, 1H), 2.5 (s, 3H), 2.49 (d, 1H), 2.44 (d, 1H), 1.47 (s, 3H), 1.32 (s, 3H). Separation by chiral HPLC provided enantiomers 17a and 17b. Optical rotations: Compound 17a, (+)50.54 (c 0.56, Chloroform, 99.31% HPLC purity); Compound 17b, (−)51.38 (c 0.55, Chloroform, 95.62% HPLC purity).

후처리

  1. customAfter consumption of starting material (by monitoring TLC and LCMS)
  2. additionthe reaction mixture was poured in to ice water
  3. extractionextracted with EtOAc (2×25 mL)
  4. washThe combined organic layer was washed with water (5×10 mL)
  5. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customthe crude product purified by reverse phase chromatography

출처 및 근거

ORD 기록
ord-c4cb0ff5b4694a8b9c0c89882f59f95c
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791132B2

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