Dimethylformamide → HCID 86716458, compound

HRID 1520243Notes

Reaction equation

HRID 1520243 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:33])([F:32])[C@:12]([C:15]2[CH:20]=[C:19]([NH:21][C:22]([C:24]3[CH:29]=[N:28][C:27](Cl)=[CH:26][N:25]=3)=[O:23])[CH:18]=[CH:17][C:16]=2[F:31])([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.CC([O-])(C)C.[K+].[CH2:46]([OH:49])[C:47]#[CH:48]>O>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1[O:9][CH2:10][C:11]([F:33])([F:32])[C@:12]([C:15]2[CH:20]=[C:19]([NH:21][C:22]([C:24]3[CH:29]=[N:28][C:27]([O:49][CH2:46][C:47]#[CH:48])=[CH:26][N:25]=3)=[O:23])[CH:18]=[CH:17][C:16]=2[F:31])([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7859Propargyl alcoholHCID 23665647Potassium tert-butoxideHCID 86716459HCID 86716459, compound

Product 1

HCID 86716458HCID 86716458, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

((R)-4-{5-[(5-Chloro-pyrazine-2-carbonyl)-amino]-2-fluoro-phenyl}-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-carbamic acid tert-butyl ester (400 mg, 800 μmol) was combined with DMF (1.2 ml) to give a colorless solution. KOtBu (180 mg, 1.6 mmol) and propargyl alcohol (449 mg, 477 μl, 8.00 mmol) were added and the reaction mixture was stirred 2 h at RT. Water was carefully added and the product was extracted with EtOAc. The organic layers were dried over Na2SO4 and concentrated under vacuum. The crude material was purified by flash chromatography (SiO2, 20 g, 0 to 50% EtOAc in heptane). Light yellow solid (350 mg, 84%). MS (ISP): m/z=520.2 [M+H]+.

Workup

  1. customto give a colorless solution
  2. extractionthe product was extracted with EtOAc
  3. dry with materialThe organic layers were dried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified by flash chromatography (SiO2, 20 g, 0 to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-f596929887794a6f8f0818d9776f84d5
Source dataset
uspto-grants-2015_07
Patent number
US09073909B2

Reaction notes

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