Water → HCID 68485737, compound

HRID 1400595Notes

Reaction equation

HRID 1400595 reaction equation
S(Cl)(Cl)=O.[CH3:5][N:6]1[CH2:34][CH2:33][C:9]2[N:10]([CH2:18][C:19]([C:22]3[CH:23]=[C:24]([CH:30]=[CH:31][CH:32]=3)[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])(O)[CH3:20])[C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][C:16]=3[C:8]=2[CH2:7]1.[OH-].[K+].O>CN1C(=O)CCC1>[CH3:5][N:6]1[CH2:34][CH2:33][C:9]2[N:10]([CH:18]=[C:19]([C:22]3[CH:23]=[C:24]([CH:30]=[CH:31][CH:32]=3)[C:25]([N:27]([CH3:28])[CH3:29])=[O:26])[CH3:20])[C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][C:16]=3[C:8]=2[CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 68486808HCID 68486808, compound

Product 1

HCID 68485737HCID 68485737, compoundYield 6.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Thionyl chloride (0.8 mL, 11.02 mmol) was added to a solution of 3-[2-(2,8-dimethyl-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)-1-hydroxy-1-methyl-ethyl]-N,N-dimethylbenzamide (500 mg, 1.23 mmol) and the reaction mixture was stirred at RT for 1 h. The solvent was removed under vacuum to obtain the crude product as a foamy solid which was dissolved in NMP (5 mL). The mixture was stirred for 5 min and powdered KOH (553 mg, 9.87 mmol) was added, and the mixture heated at 85° C. for 45 min. After completion of reaction, the mixture was poured into water and extracted with EtOAc (3×30 mL). The organic layer washed with water, dried over sodium sulfate and concentrated under vacuum to obtain the crude product (600 mg) which was purified by reverse phase HPLC to yield 3-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-methyl-vinyl]-N,N-dimethyl-benzamide (30 mg) as free base. 1H NMR (CD3OD, oxalate salt) δ (ppm): 7.76 (d, 1H), 7.70 (s, 1H), 7.52 (t, 1H), 7.44 (d, 1H), 7.30 (s, 1H), 7.18-7.06 (m, 3H), 4.58 (m, 2H), 3.70 (m, 2H), 3.18 (m, 2H), 3.12 (s, 6H), 3.05 (s, 3H), 2.42 (s, 3H), 1.98 (s, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. customto obtain the crude product as a foamy solid which
  3. stirringThe mixture was stirred for 5 min
  4. temperaturethe mixture heated at 85° C. for 45 min
  5. customAfter completion of reaction
  6. extractionextracted with EtOAc (3×30 mL)
  7. washThe organic layer washed with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customto obtain the crude product (600 mg) which
  11. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-c84989f5de234ec3b83909763361e048
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

Loading…