Carbon Dioxide → HCID 86673734, compound

HRID 1626157Notes

Reaction equation

HRID 1626157 reaction equation
[F:1][C:2]1([F:27])[CH2:7][O:6][C:5]([NH2:8])=[N:4][C@:3]1([CH3:26])[C:9]1[CH:10]=[N:11][N:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[C:21][Si](C)(C)C)[CH:15]=2)[CH:13]=1.C[O-].[Na+].C(=O)=O>CO.O.ClCCl>[C:20]([C:16]1[CH:15]=[C:14]([N:12]2[CH:13]=[C:9]([C@:3]3([CH3:26])[C:2]([F:1])([F:27])[CH2:7][O:6][C:5]([NH2:8])=[N:4]3)[CH:10]=[N:11]2)[CH:19]=[CH:18][CH:17]=1)#[CH:21]

Participants

7

Reactant 3

HCID 280Carbon DioxideHCID 10942334Sodium MethoxideHCID 71008715HCID 71008715, compound

Product 1

HCID 86673734HCID 86673734, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-5,5-difluoro-4-methyl-4-(1-(3-((trimethylsilyl)ethynyl)phenyl)-1H-pyrazol-4-yl)-5,6-dihydro-4H-1,3-oxazin-2-amine (68.6 mg, 177 μmol) in methanol (2 ml) was treated at room temperature with sodium methoxide (5.4M in methanol; 1 μl, 5.4 μmol). After 90 minutes a small quantity of dry ice was added to neutralize the reaction mixture. After evaporation at reduced pressure the residue thus obtained was dissolved in a mixture of water and dichloromethane. The aqueous layer was extracted with dichloromethane, thereafter, the combined organic layers were washed with water, dried over sodium sulphate, and evaporated. The residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent. The (R)-4-[1-(3-ethynyl-phenyl)-1H-pyrazol-4-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (29 mg, 52% yield) was obtained as a light yellow solid. MS (ISP): m/z=317.1 [M+H]+.

Workup

  1. customAfter evaporation at reduced pressure the residue
  2. customthus obtained
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washthe combined organic layers were washed with water
  5. dry with materialdried over sodium sulphate
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent

Sources & evidence

ORD record
ord-5ab67b3c89f546c0a130191aeec27535
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

Loading…