Water → 1-(9-Chloro-3-methyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-ol

HRID 1481415Notes

Reaction equation

HRID 1481415 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][C:7]=3[C:6]=2[CH:5]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([CH3:29])[CH2:28][O:27]2)=[CH:22][CH:21]=1.O>CN(C=O)C>[Cl:3][C:4]1[CH:12]=[CH:11][C:10]2[N:9]([CH2:29][C:26]([C:23]3[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=3)([OH:27])[CH3:28])[C:8]3[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17][C:7]=3[C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 178694862-(4-Fluorophenyl)-2-methyloxiraneHCID 685585079-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 593681551-(9-Chloro-3-methyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-olYield 45.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared by following general procedure 5. To a stirred suspension of sodium hydride (61 mg, 0.254 mmol) in 5 mL of DMF, 9-chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.2 g, 0.852 mmol) was added and stirred at RT for 5 min. 2-(4-Fluorophenyl)-2-methyloxirane (194 mg, 1.27 mmol) was added slowly dropwise and stirred at RT for 14 h. The reaction was monitored by TLC and LCMS. After completion of the reaction, water was added, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, evaporated under reduced pressure and purified by reverse phase chromatography to afford 150 mg of (1-(9-chloro-3-methyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl)propan-2-ol) as the TFA salt. 1H NMR (DMSO-d6, TFA salt) δ (ppm): 7.40 (s, 1H), 7.30-7.18 (m, 3H), 7.0-6.80 (m, 3H), 4.40-4.25 (d, 2H), 4.25-4.15 (d, 2H), 3.40-3.20 (d, 2H), 3.20-3.00 (m, 4H), 2.90 (s, 3H), 1.50 (s, 3H).

Workup

  1. customThe title compound was prepared
  2. additionwas added
  3. stirringstirred at RT for 14 h
  4. additionwas added
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customevaporated under reduced pressure
  8. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-36844d4db92d426993d32aafbaee512d
Source dataset
uspto-grants-2016_08
Patent number
US09409910B2

Reaction notes

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