Trifluoroacetic acid → 5-Cyano-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

HRID 2196343Notes

Reaction equation

HRID 2196343 reaction equation
C(OC(=O)[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:34])([CH:14]([F:16])[F:15])[N:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:34])([CH:14]([F:16])[F:15])[N:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66665639((R)-5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 581188885-Cyano-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

((R)-5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester (44.47 g, 91.0 mmol) was dissolved in 450 ml DCM and mildly chilled with a rt water bath. TFA (150 ml) was added. The reaction was slightly exothermic. The mixture was stirred for 1.5 h at rt. The volatiles were removed with vacuum at rt. The residue was taken up in DCM and the procedure repeated twice. The residue was taken up in 3 L EtOAc and washed with 10% aqueous Na2CO3 and brine. The organic phase was dried with sodium sulfate and partially evaporated. iPrOH was added and the mixture chilled. The title compound was collected as snow-white crystals. Yield 30.56 g.

Workup

  1. customThe volatiles were removed with vacuum at rt
  2. washwashed with 10% aqueous Na2CO3 and brine
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. custompartially evaporated
  5. additioniPrOH was added
  6. temperaturethe mixture chilled
  7. customThe title compound was collected as snow-white crystals

Sources & evidence

ORD record
ord-54292edb45784be3a86f1e541a76e14f
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

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