Trifluoroacetic acid → HCID 178523573, compound

HRID 539914Notes

Reaction equation

HRID 539914 reaction equation
[F:1][C:2]1[C:3]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][C@@H:40]([NH:44][C:45](N3CCCC3)=[O:46])[CH2:39]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[N:10](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:9]=2)=[N:6][CH:7]=1.C([SiH]([CH2:57][CH3:58])CC)C.F[C:60](F)(F)[C:61](O)=O.[C:66]([O-])(O)=O.[Na+]>ClCCl>[F:1][C:2]1[C:3]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][C@@H:40]([NH:44][C:45]([CH:58]3[CH2:57][CH2:61][CH2:60][CH2:66]3)=[O:46])[CH2:39]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[C:14]([F:17])[CH:15]=3)[NH:10][N:9]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 86707189HCID 86707189, compound

Product 1

HCID 178523573HCID 178523573, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-[(1R,3S)-3-[[5-fluoro-2-(5-fluoro-1-trityl-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl]amino]cyclohexyl]pyrrolidine-1-carboxamide, 22, (0.100 g, 0.146 mmol) in dichloromethane (5 mL) was added triethylsilane (0.350 mL, 2.190 mmol) followed by trifluoroacetic acid (0.337 mL, 4.380 mmol). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted into 30 ml CH2Cl2 and aqueous saturated NaHCO3 solution. The organic phase was washed with brine, dried over MgSO4 and the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (12% MeOH and 88% CH2Cl2) to afford 64 mg of the desired product: 1H NMR (300 MHz, CDCl3) δ 8.42 (dd, J=2.7, 1.4 Hz, 1H), 7.90 (d, J=3.2 Hz, 1H), 7.51 (dd, J=8.6, 2.7 Hz, 1H), 5.15 (d, J=5.5 Hz, 1H), 4.26 (d, J=7.9 Hz, 1H), 3.99-3.79 (m, 1H), 3.38 (d, J=3.2 Hz, 4H), 3.09 (d, J=6.6 Hz, 1H), 2.82 (d, J=11.3 Hz, 1H), 2.16-2.05 (m, 1H), 2.01-1.85 (m, 5H), 1.78 (d, J=13.2 Hz, 1H), 1.32-1.04 (m, 4H), 0.92 (dd, J=21.7, 11.8 Hz, 1H); LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=2.31 min, (M+H) 443.34.

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe crude residue was purified by silica gel chromatography (12% MeOH and 88% CH2Cl2)

Sources & evidence

ORD record
ord-7f9f77c2e43143d184d4a02c72874bf3
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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