Trifluoroacetic acid → N-[(4'R)-2''-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-6'-yl]-5-(difluoromethyl)pyrazine-2-carboxamide

HRID 594914Notes

Reaction equation

HRID 594914 reaction equation
C(OC(=O)[NH:7][C:8]1[O:9][CH2:10][C@@:11]2([C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH:22][C:23]([C:25]4[CH:30]=[N:29][C:28]([CH:31]([F:33])[F:32])=[CH:27][N:26]=4)=[O:24])[CH:20]=3)[O:15][C:14]([CH3:35])([CH3:34])[C:13]32[CH2:37][CH2:36]3)[N:12]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[NH2:7][C:8]1[O:9][CH2:10][C@@:11]2([C:21]3[C:16](=[CH:17][CH:18]=[C:19]([NH:22][C:23]([C:25]4[CH:30]=[N:29][C:28]([CH:31]([F:33])[F:32])=[CH:27][N:26]=4)=[O:24])[CH:20]=3)[O:15][C:14]([CH3:35])([CH3:34])[C:13]32[CH2:37][CH2:36]3)[N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86724286tert-butyl [(4'R)-6'-({[5-(difluoromethyl)pyrazin-2-yl]carbonyl}amino)-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamate

Product 1

HCID 86724318N-[(4'R)-2''-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-6'-yl]-5-(difluoromethyl)pyrazine-2-carboxamideYield 83.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of tert-butyl[(4′R)-6′-({[5-(difluoromethyl)pyrazin-2-yl]carbonyl}amino)-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (373 mg, 0.704 mmol) in chloroform (6 ml) was added trifluoroacetic acid (2 ml). The mixture was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was purified by silica gel column chromatography (precolumn: NH-silica gel, main column: neutral silica gel, chloroform/methanol=100:0-10:1). To the purified product was added a mixture of hexane and ethyl acetate (4:1), and the mixture was stirred at room temperature over night. The resulting precipitate was collected, washed with a mixture of hexane and ethyl acetate (4:1), and dried in vacuo to afford N-[(4′R)-2″-amino-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-6′-yl]-5-(difluoromethyl)pyrazine-2-carboxamide (253 mg).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by silica gel column chromatography (precolumn: NH-silica gel, main column: neutral silica gel, chloroform/methanol=100:0-10:1)
  3. additionTo the purified product was added
  4. additiona mixture of hexane and ethyl acetate (4:1)
  5. stirringthe mixture was stirred at room temperature over night
  6. customThe resulting precipitate was collected
  7. washwashed with a mixture of hexane and ethyl acetate (4:1)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-71519b659ee74cebab0fa4315df5b62d
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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