Phosphorus oxychloride → HCID 90041143, compound

HRID 1485901Notes

Reaction equation

HRID 1485901 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:18])[CH:14]=2)[CH:9]1[C:19](O)=[O:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:24]=1[NH2:25].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:18])[CH:14]=2)[CH:9]1[C:19](=[O:20])[NH:25][C:24]1[C:23]([F:22])=[CH:29][CH:28]=[CH:27][C:26]=1[F:30])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 796472,6-DifluoroanilineHCID 573679552-(tert-Butoxycarbonyl)-6-fluoro-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

Product 1

HCID 90041143HCID 90041143, compoundYield 42.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 6-fluoro-3,4-dihydro-1H-isoquinoline-1,2-dicarboxylic acid 2-tert-butyl ester (0.37 g, 1.25 mmol, Eq: 1.00) and 2,6-difluoroaniline (194 mg, 162 μl, 1.5 mmol, Eq: 1.2) in Pyridine (7 mL) at 0° C. was added phosphorus oxychloride (288 mg, 175 μl, 1.88 mmol, Eq: 1.5). The reaction was warmed to RT, stirred for 18 h, diluted with water and extracted with EtOAc. The combined organics were washed with 1 N HCl, water, brine, dried with Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography to afford 0.2181 g 1-(2,6-difluoro-phenylcarbamoyl)-6-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester as white foam. 42.8% MS m/z 428.9 (M+H)

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organics were washed with 1 N HCl, water, brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-f775e778bff746189691d988453cd77f
Source dataset
uspto-grants-2016_08
Patent number
US09422332B2

Reaction notes

Loading…