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 1630488Notes

Reaction equation

HRID 1630488 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c4cb0ff5b4694a8b9c0c89882f59f95c
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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