HCID 87467106, compound → HCID 59455153, compound

HRID 1401670Notes

Reaction equation

HRID 1401670 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:9][N:10]1[CH2:28][CH2:27][C:13]2[N:14]([C:22]([CH3:26])([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[CH2:28][CH2:27][C:13]2[N:14]([C:22]([CH3:25])([CH3:26])[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 87467106HCID 87467106, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 59455153HCID 59455153, compoundYield 47.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phenyl magnesium bromide (1M solution in THF) (3.7 mL, 3.69 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)-2-methyl-propionaldehyde (200 mg, 0.73 mmol) in THF (30 mL). The contents were stirred at RT for 16 h, diluted with EtOAc (50 mL) and water (40 mL). The layers were separated and the aqueous layer was again extracted with EtOAc (2×50 mL). The combined organic extracts were dried over sodium sulfate and concentrated under vacuum to obtain crude compound (300 mg), which was purified by column chromatography on silica gel (100-200 mesh) [Eluent: 0-5% MeOH in DCM] to afford 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-methyl-1-phenyl-propan-1-ol (120 mg) which was repurified by prep. TLC to yield free base (25 mg) compound. The free base was converted into the HCl salt. 1H NMR (CD3OD, HCl salt) δ (ppm): 7.80 (m, 1H), 7.25-7.0 (m, 6H), 6.80 (d, 1H), 5.58 (s, 1H), 4.40 (m, 2H), 3.50 (m, 2H), 2.95 (s, 3H), 2.42 (s, 3H), 2.0 (s, 3H), 1.64 (s, 3H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was again extracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customto obtain crude compound (300 mg), which
  6. customwas purified by column chromatography on silica gel (100-200 mesh) [Eluent: 0-5% MeOH in DCM]

Sources & evidence

ORD record
ord-72963f4663364654911217c0c01c6dd3
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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