Trifluoroacetic acid → HCID 178445893, compound

HRID 1055107Notes

Reaction equation

HRID 1055107 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@@H:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][C:20]([OH:22])=[O:21])[CH:14]=[CH:13][N:12]=3)=[N:9][N:8](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:5]2=[N:6][CH:7]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:17][C@@H:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][C:20]([OH:22])=[O:21])[CH:14]=[CH:13][N:12]=3)=[N:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 71247582HCID 71247582, compound2×

Product 1

HCID 178445893HCID 178445893, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude (R)-3-((2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoic acid, 138a, (0.11 g, 0.21 mmol) in CH2Cl2 was added triethylsilane (0.15 mL, 0.94 mmol) followed by trifluoroacetic acid (0.15 mL, 1.95 mmol). After stirring the resulting solution at room temperature for 1 hour, the reaction mixture was kept below 5° C. overnight (refrigerator). The mixture was then allowed to warm to room temperature and kept at that temperature for an additional 5 hours. The solution was diluted with toluene and concentrated in vacuo. Trituration with Et2O followed by preparative HPLC purification provided 15 mg of the desired product as the TFA salt. 1H NMR indicated a 3 to 1 mixture of atropisomers: 1H NMR (400 MHz, MeOD, major isomer) δ 8.63-8.45 (m, 2H), 7.96 (d, J=7.3 Hz, 2H), 6.66 (d, J=7.3 Hz, 2H), 4.95 (d, J=10.6 Hz, 2H), 2.84 (dd, J=15.4, 2.4 Hz, 2H), 2.44 (dd, J=15.9, 10.7 Hz, 2H), 0.98 (s, 9H); LCMS Gradient 10-90%, 0.1% trifluoroacetic acid, 5 minutes, C18/ACN, Retention Time=2.12 minutes (M+H) 359.02.

Workup

  1. waitthe reaction mixture was kept below 5° C. overnight
  2. temperatureto warm to room temperature
  3. waitkept at that temperature for an additional 5 hours
  4. concentrationconcentrated in vacuo
  5. customTrituration with Et2O followed by preparative HPLC purification

Sources & evidence

ORD record
ord-85bd33ca10b34780b7c33ca3c61d5fa8
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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