Trifluoroacetic acid → HCID 178496842, compound

HRID 539923Notes

Reaction equation

HRID 539923 reaction equation
[Cl:1][C:2]1[C:3]([NH:37][CH:38]2[CH:43]3[CH2:44][CH2:45][CH:40]([CH2:41][CH2:42]3)[CH:39]2[C:46]([O:48][CH3:49])=[O:47])=[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.[SiH](CC)(CC)CC.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:37][CH:38]2[CH:43]3[CH2:42][CH2:41][CH:40]([CH2:45][CH2:44]3)[CH:39]2[C:46]([O:48][CH3:49])=[O:47])=[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

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86707193methyl 3-((5-chloro-2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylate

Product 1

HCID 178496842HCID 178496842, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (+/−)-trans-(2,3)-methyl 3-((5-chloro-2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylate, 38, (0.85 g, 1.26 mmol) in CH2Cl2 (42.5 mL) at room temperature was added Et3SiH (1.00 mL, 6.32 mmol) followed by trifluoroacetic acid (0.97 mL, 12.60 mmol). The reaction was stirred at room temperature. After the reaction was complete, as judged by LC-MS, the solution was concentrated in vacuo. Careful flash chromatography (SiO2, 0-7% MeOH—CH2Cl2, gradient elution) provided the desired product (373 mg, 66% yield)L 1H NMR (400 MHz, MeOD) δ 8.66 (dd, J=8.3, 2.5 Hz, 1H), 8.53 (s, 1H), 8.28 (s, 1H), 5.05 (d, J=6.5 Hz, 1H), 3.69 (s, 3H), 2.95 (d, J=6.8 Hz, 1H), 2.09 (s, 1H), 1.98 (s, 1H), 1.96-1.79 (m, 3H), 1.77-1.61 (m, 3H), 1.61-1.45 (m, 2H); LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=2.55 min, (M+H) 431.14.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. washCareful flash chromatography (SiO2, 0-7% MeOH—CH2Cl2, gradient elution)

Sources & evidence

ORD record
ord-0129d3f8c762468196d285fdf8781f05
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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