Trifluoroacetic acid → HCID 44556179, compound

HRID 221998Notes

Reaction equation

HRID 221998 reaction equation
[NH2:1][C:2]1[N:14]2[C:5]([C:6]3[CH:7]=[C:8]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:9]([C:15]4[CH:20]=[CH:19][C:18]([C:21]5([NH:27]C(=O)OC(C)(C)C)[CH2:24][C:23]([F:26])([F:25])[CH2:22]5)=[CH:17][CH:16]=4)=[N:10][C:11]=3[CH:12]=[CH:13]2)=[N:4][N:3]=1.C(O)(C(F)(F)F)=O>C(Cl)(Cl)Cl>[NH2:27][C:21]1([C:18]2[CH:17]=[CH:16][C:15]([C:9]3[C:8]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[CH:7][C:6]4[C:5]5=[N:4][N:3]=[C:2]([NH2:1])[N:14]5[CH:13]=[CH:12][C:11]=4[N:10]=3)=[CH:20][CH:19]=2)[CH2:24][C:23]([F:25])([F:26])[CH2:22]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58229877HCID 58229877, compound

Product 1

HCID 44556179HCID 44556179, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of {1-[4-(3-amino-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]-3,3-difluorocyclobutyl}carbamate (5-18) (4 mg, 0.007 mmol) in CHCl3 (0.5 mL) was added TFA (0.5 mL), and the mixture was stirred at room temperature for 1 hour. The solvent was concentrated under reduced pressure and the residue was purified by reverse phase column chromatography (Sunfire C18) eluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were free based by suspending in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 8-[4-(1-amino-3,3-difluorocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3-amine (5-19) as a yellow oil. HRMS (M+H)+: observed=443.1796, calculated=443.1801.

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. customthe residue was purified by reverse phase column chromatography (Sunfire C18)
  3. washeluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient
  4. washwashed with a saturated solution of sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b177f66f2d6249e4a1d8031485ec2177
Source dataset
uspto-grants-2012_06
Patent number
US08207169B2

Reaction notes

Loading…