Dimethyl Sulfoxide → HCID 53890318, compound

HRID 263543Notes

Reaction equation

HRID 263543 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]1([C:17]2[C:25]([CH:26]=[CH:27][C:28]([N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][C@@H:31]3[CH2:36][CH2:37][OH:38])=[O:29])=[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][N:19]3[N:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>C(Cl)Cl.C(N(CC)CC)C>[C:11]1([C:17]2[C:25]([CH:26]=[CH:27][C:28]([N:30]3[CH2:35][CH2:34][CH2:33][CH2:32][C@@H:31]3[CH2:36][CH:37]=[O:38])=[O:29])=[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][N:19]3[N:18]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 129453HCID 129453, compound

Product 1

HCID 53890318HCID 53890318, compoundYield 38.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of dimethyl sulfoxide (202 mg) in methylene chloride (1.0 ml) was added dropwise to a solution of oxalyl dichloride (247 mg) in methylene chloride (10 ml) over 5 minutes at -78° C. After 10 minutes, a solution of (2R)-1-[3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2-(2-hydroxyethyl)piperidine (trans isomer) (364 mg) in methylene chloride (3.4 mg) was added dropwise over 10 minutes at -78° C. The solution was stirred at -78° C. for 20 minutes and at -45° C. for 1 hour. Triethylamine (986 μl) was added to the solution and the mixture was stirred at -20°~0° C. for 20 minutes. Saturated ammonium chloride solution (20 ml) was added to the reaction mixture was the mixture was extracted with methylene chloride (10 ml×2). The combined extracts were washed with brine (10 ml), dried over magnesium sulfate and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (10 g) with a mixture of methylene chloride and ethyl acetate (10:1) as an eluent to give (2R)-1-[3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2-(formylmethyl)piperidine (trans isomer) (139.0 mg) as an oil.

Workup

  1. stirringthe mixture was stirred at -20°~0° C. for 20 minutes
  2. extractionwas extracted with methylene chloride (10 ml×2)
  3. washThe combined extracts were washed with brine (10 ml)
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe crude material was purified by column chromatography on silica gel (10 g) with a mixture of methylene chloride and ethyl acetate (10:1) as an eluent

Sources & evidence

ORD record
ord-0243842debe24a93afd3c83bc3407ac2
Source dataset
uspto-grants-1997_07
Patent number
US05643938

Reaction notes

Loading…