Trifluoroacetic acid → HCID 118307530, compound

HRID 530403Notes

Reaction equation

HRID 530403 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=O.[NH2:8][C:9]1[CH:10]=[C:11]([C:26]2[CH:31]=[CH:30][C:29]([C@@H:32]([OH:36])[CH:33]([F:35])[F:34])=[CH:28][CH:27]=2)[CH:12]=[C:13]([NH:15][C:16]2[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=2)[CH:14]=1.C([BH3-])#N.[Na+].FC(F)(F)C=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[F:34][CH:33]([F:35])[C@@H:32]([C:29]1[CH:28]=[CH:27][C:26]([C:11]2[CH:12]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][N:17]=3)[CH:14]=[C:9]([NH:8][CH2:3][C:2]([F:7])([F:6])[F:1])[CH:10]=2)=[CH:31][CH:30]=1)[OH:36]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 65564TrifluoroacetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 73295140HCID 73295140, compound

Product 1

HCID 118307530HCID 118307530, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a cooled (0° C.) mixture of (1R)-1-(3′-amino-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-yl)-2,2-difluoroethanol (100 mg, 0.244 mmol) and sodium cyanoborohydride (30.6 mg, 0.487 mmol) in dichloromethane (0.5 mL) at 0° C. Trifluoroacetaldehyde (85 mg, 0.731 mmol) was added to the reaction mixture, and then stirred at room temperature for 3 hours. Aqueous sodium carbonate was added to the reaction mixture, extracted with ethyl acetate and the combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) to give (1R)-2,2-difluoro-1-(3′-[(2,2,2-trifluoroethyl)amino]-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-yl)ethanol as a yellow solid. MS ESI calc'd. for C21H17F8N4O [M+H] 493. found 493. 1H NMR (400 MHz, CDCl3): δ 8.66 (d, J=5.0 Hz, 1H); 7.70 (s, 1H); 7.63 (d, J=8.0 Hz, 2H); 7.52 (d, J=8.0 Hz, 2H); 7.39 (s, 1H); 7.13 (s, 1H); 7.08 (d, J=5.0 Hz, 1H); 6.65 (s, 1H); 5.83 (td, J=56.0, 4.8 Hz, 1H); 4.91 (td, J=10.1, 4.8 Hz, 1H); 3.87 (q, J=8.9 Hz, 2H).

Workup

  1. temperaturea cooled
  2. extractionextracted with ethyl acetate
  3. concentrationthe combined organic layers were concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ea958e99f43d4919bfa2bb7769d59f65
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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