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 873767Notes

Reaction equation

HRID 873767 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[CH:5][C:6]([C:9]([NH:11][C:12]2[CH:13]=[C:14]3[C@@:23]4([CH2:27][O:26][C:25]([NH:28]C(=O)OC(C)(C)C)=[N:24]4)[C:20]4([CH2:22][CH2:21]4)[C:19]([CH3:37])([CH3:36])[O:18][C:15]3=[CH:16][CH:17]=2)=[O:10])=[N:7][CH:8]=1.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[NH2:28][C:25]1[O:26][CH2:27][C@@:23]2([C:14]3[C:15](=[CH:16][CH:17]=[C:12]([NH:11][C:9]([C:6]4[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:8][N:7]=4)=[O:10])[CH:13]=3)[O:18][C:19]([CH3:36])([CH3:37])[C:20]32[CH2:21][CH2:22]3)[N:24]=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-methoxypyrazine-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-4ea0c9f137434d5993d7814519511d23
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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