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 1469588Notes

Reaction equation

HRID 1469588 reaction equation
[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

Participants

5

Reactant 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

Product 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-ethanolYield 43.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2080fda6e327428eb48a4097d0eefc9c
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

Loading…