2,2,2-Trifluoroethanol → HCID 117653897, compound

HRID 530121Notes

Reaction equation

HRID 530121 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[N+:14]([O-:18])[CH:15]=[CH:16][CH:17]=3)[C:7](=[O:19])[C@@H:6]([CH3:20])[N:5]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:4]=2[N:3]=1.[F:27][C:28]1[CH:29]=[C:30]([NH2:37])[CH:31]=[C:32]2[C:36]=1[NH:35][N:34]=[CH:33]2.C(O)C(F)(F)F.FC(F)(F)C(O)=O>>[CH:21]1([N:5]2[C:4]3[N:3]=[C:2]([NH:37][C:30]4[CH:31]=[C:32]5[C:36](=[C:28]([F:27])[CH:29]=4)[NH:35][N:34]=[CH:33]5)[N:11]=[CH:10][C:9]=3[N:8]([C:12]3[CH:13]=[N+:14]([O-:18])[CH:15]=[CH:16][CH:17]=3)[C:7](=[O:19])[C@H:6]2[CH3:20])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 6422Trifluoroacetic acid2×HCID 68672578HCID 68672578, compound2×HCID 89560847HCID 89560847, compound

Product 1

HCID 117653897HCID 117653897, compoundYield 24%

Conditions

Temperature
100 °C

Procedure

To a solution of (7R)-2-chloro-8-cyclohexyl-7-methyl-5-(1-oxidopyridin-3-yl)-7,8-dihydropteridin-6(5H)-one (30.4 mg, 0.081 mmol) and 7-fluoro-1H-indazol-5-amine (37.2 mg, 0.25 mmol) in trifluoroethanol (2.0 mL, 27 mmol) in a microwave reactor vial was added trifluoroacetic acid (42 mg, 0.37 mmol). The vial was then sealed, and the mixture was stirred at 100° C. (oil bath). More 7-fluoro-1H-indazol-5-amine (29.5 mg, 0.195 mmol) and trifluoroacetic acid (0.025 mL, 0.32 mmol) was added after 15 h, and heating at 100° C. was continued for additional 24 h. The reaction mixture was cooled to rt and quenched with saturated aq. NaHCO3 solution (5 mL). The resulting mixture was extracted with 5% MeOH in dichloromethane (15 mL×4). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a crude residue, which was then purified by silica gel column chromatography (eluent: 8% methanol in dichloromethane) to give the desired product (24%).

Workup

  1. customThe vial was then sealed
  2. temperatureheating at 100° C.
  3. temperatureThe reaction mixture was cooled to rt
  4. customquenched with saturated aq. NaHCO3 solution (5 mL)
  5. extractionThe resulting mixture was extracted with 5% MeOH in dichloromethane (15 mL×4)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a crude residue, which
  11. customwas then purified by silica gel column chromatography (eluent: 8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9e39055bf6c24eddb3b6318b857f8aa5
Source dataset
uspto-grants-2016_05
Patent number
US09351974B2

Reaction notes

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