Hexafluoroacetylacetone → 2-[4,6-Bis(trifluoromethyl)pyrimidin-2-yl]-5-{[2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}octahydropyrrolo[3,4-c]pyrrole

HRID 244031Notes

Reaction equation

HRID 244031 reaction equation
OC(C(F)(F)F)=O.[F:8][C:9]1[CH:27]=[CH:26][CH:25]=[C:24]([N:28]2[N:32]=[CH:31][CH:30]=[N:29]2)[C:10]=1[C:11]([N:13]1[CH2:17][CH:16]2[CH2:18][N:19]([C:21](=[NH:23])[NH2:22])[CH2:20][CH:15]2[CH2:14]1)=[O:12].C[O-].[Na+].[F:36][C:37]([F:48])([F:47])[C:38](=O)[CH2:39][C:40](=O)[C:41]([F:44])([F:43])[F:42]>C(O)CCC>[F:36][C:37]([F:47])([F:48])[C:38]1[CH:39]=[C:40]([C:41]([F:42])([F:43])[F:44])[N:22]=[C:21]([N:19]2[CH2:18][CH:16]3[CH:15]([CH2:14][N:13]([C:11]([C:10]4[C:24]([N:28]5[N:32]=[CH:31][CH:30]=[N:29]5)=[CH:25][CH:26]=[CH:27][C:9]=4[F:8])=[O:12])[CH2:17]3)[CH2:20]2)[N:23]=1

Participants

5

Reactant 3

HCID 73706HexafluoroacetylacetoneHCID 10942334Sodium MethoxideHCID 866691735-(2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl)hexahydro-pyrrolo[3,4-c]pyrrole-2(1H)-carboximidamide TFA salt

Product 1

HCID 849729832-[4,6-Bis(trifluoromethyl)pyrimidin-2-yl]-5-{[2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}octahydropyrrolo[3,4-c]pyrroleYield 6.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

Crude 5-(2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoyl)hexahydro-pyrrolo[3,4-c]pyrrole-2(1H)-carboximidamide—TFA salt (66 mg) was diluted with n-butanol (4 mL) and treated with sodium methoxide (51.9 mg, 0.961 mmol). The reaction is heated to reflux for 1 hour, then cooled and 1,1,1,5,5,5-hexafluoropentane-2,4-dione (400 mg, 1.92 mmol) is added prior to re-heating the reaction to reflux for 19 hours. The mixture was then cooled and concentrated, then diluted with DCM and saturated sodium bicarbonate. Extract with DCM and concentrate. Reverse phase HPLC gave the title compound (4.6 mg). MS (ESI): mass calculated for C21H16F7N7O, 515.39; m/z found 416.2 [M+H]+. Rotamers observed in 1H NMR.

Workup

  1. temperatureThe reaction is heated
  2. temperatureto reflux for 1 hour
  3. temperaturecooled
  4. temperatureto re-heating
  5. customthe reaction
  6. temperatureto reflux for 19 hours
  7. temperatureThe mixture was then cooled
  8. concentrationconcentrated
  9. additiondiluted with DCM and saturated sodium bicarbonate
  10. extractionExtract with DCM
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-07bf3e8fd9db4b8ead0e90368f7d35b3
Source dataset
uspto-grants-2014_02
Patent number
US08653263B2

Reaction notes

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