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

HRID 594913Notes

Reaction equation

HRID 594913 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]([O:31][CH3:32])=[CH:27][N:26]=4)=[O:24])[CH:20]=3)[O:15][C:14]([CH3:34])([CH3:33])[C:13]32[CH2:36][CH2:35]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]([O:31][CH3:32])=[CH:27][N:26]=4)=[O:24])[CH:20]=3)[O:15][C:14]([CH3:33])([CH3:34])[C:13]32[CH2:35][CH2:36]3)[N:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86724285tert-butyl [(4'R)-6'-{[(5-methoxypyrazin-2-yl)carbonyl]amino}-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamate

Product 1

HCID 86724317N-[(4'R)-2''-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-6'-yl]-5-me thoxypyrazine-2-carboxamideYield 78.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of tert-butyl[(4′R)-6′-{[(5-methoxypyrazin-2-yl)carbonyl]amino}-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (392 mg, 0.769 mmol) in chloroform (3 ml) was added trifluoroacetic acid (1.8 ml), and the mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo, and the residue was purified by silica gel column chromatography (precolumn: NH-silica gel, main column: neutral silica gel, chloroform/methanol=10:0-10:1). To the purified product was added a mixture of hexane/ethyl acetate (4:1) and the mixture was stirred at room temperature over night. The precipitate was collected, washed with mixture of hexane/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-me thoxypyrazine-2-carboxamide (246 mg).

Workup

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

Sources & evidence

ORD record
ord-7a26587425c445d9947504873f8015a1
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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