HCID 86677147, compound → HCID 59455003, compound

HRID 1630598Notes

Reaction equation

HRID 1630598 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][N:10]1[CH2:27][CH2:26][C:13]2[N:14]([CH:22]([CH3:25])[CH:23]=[O:24])[C:15]3[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][C:20]=3[C:12]=2[CH2:11]1>C1COCC1.CCOC(C)=O.O>[CH3:9][N:10]1[CH2:27][CH2:26][C:13]2[N:14]([CH:22]([CH3:25])[CH:23]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[OH:24])[C:15]3[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][C:20]=3[C:12]=2[CH2:11]1

Participants

6

Reactant 2

HCID 86677147HCID 86677147, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 59455003HCID 59455003, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phenyl magnesium bromide (1M solution in THF) (6.24 mL, 6.24 mmol) was added dropwise at −70° C. to a stirred solution of 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-propionaldehyde (400 mg, 1.56 mmol) in THF (40 mL), the reaction mixture stirred at RT for 16 h, diluted with EtOAc (75 mL) and water (60 mL). The two layers were separated, the aq. layer extracted with EtOAc (2×75 mL), and the combined organic layers dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude (500 mg) was purified by prep. HPLC to afford 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)1-phenyl-propan-1-ol yielded as the TFA salt (65 mg). 1H NMR (CDCl3, Free base) δ (ppm): 7.37 (d, 1H), 7.17 (t, 3H), 7.12 (s, 1H), 7.06 (m, 2H), 6.95 (d, 1H), 5.11 (t, 1H), 4.37 (t, 1H), 3.57 (dd, 1H), 3.46 (d, 1H), 2.67 (m, 2H), 2.51 (m, 1H), 2.43 (s, 3H), 2.41 (s, 3H), 1.68 (d, 3H). Separation by chiral HPLC provides diastereomers II-95a-d.

Workup

  1. customThe two layers were separated
  2. extractionthe aq. layer extracted with EtOAc (2×75 mL)
  3. dry with materialthe combined organic layers dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude (500 mg) was purified by prep

Sources & evidence

ORD record
ord-c921ecc8a79948c6b92af22fbc79fa72
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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