HCID 178418546, compound → HCID 178433007, compound

HRID 1367033Notes

Reaction equation

HRID 1367033 reaction equation
Br[C:2]1[CH:32]=[CH:31][C:5]2[NH:6][C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][N:11]3[C:16]([C:18]3[N:19]=[C:20]([CH3:30])[S:21][C:22]=3[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:17])=[N:8][C:4]=2[CH:3]=1.[Cu][C:34]#[N:35]>CN1CCCC1=O.O.C(OCC)(=O)C>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:22]2[S:21][C:20]([CH3:30])=[N:19][C:18]=2[C:16]([N:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH:10]2[CH2:9][C:7]2[NH:6][C:5]3[CH:31]=[CH:32][C:2]([C:34]#[N:35])=[CH:3][C:4]=3[N:8]=2)=[O:17])=[CH:28][CH:27]=1

Participants

5

Reactant 2

HCID 178418546HCID 178418546, compoundHCID 178433006HCID 178433006, compound

Product 1

HCID 178433007HCID 178433007, compoundYield 1%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
200 °C

Procedure

A stirring mixture of (RS)-1-[2-(5-bromo-1H-benzoimidazol-2-ylmethyl)-piperidin-1-yl]-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone, E34 (25 mg, 0.44 mmol) and copper(I) cyanide (79 mg, 0.88 mmol) in N-methylpyrrolidinone (7 ml) under argon was heated at 200° C. for 5 h. The cooled reaction mixture was diluted with water/ethyl acetate and filtered through Kieselghur. The organic phase was washed with water (2×), brine (2×), dried (MgSO4) and the solvent removed in vacuo. The residue was chromatographed (silica gel, 0-4% methanol (containing 10%. 0.880 ammonia)-dichloromethane). Further purification by HPLC (Supercosil ABZ+, 5-95% acetonitrile containing 0.1% trifluoroacetic acid-water containing 0.1% trifluoroacetic acid) afforded the title compound as a pale brown gum (2 mg, 1%).

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered through Kieselghur
  3. washThe organic phase was washed with water (2×), brine (2×)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customThe residue was chromatographed (silica gel, 0-4% methanol (containing 10%. 0.880 ammonia)-dichloromethane)
  7. customFurther purification by HPLC (Supercosil ABZ+, 5-95% acetonitrile containing 0.1% trifluoroacetic acid-water containing 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-cf8dd3a6f0904d64ac338bba6d7cca35
Source dataset
uspto-grants-2011_02
Patent number
US07893090B2

Reaction notes

Loading…