Trifluoroacetic acid → HCID 178496844, compound

HRID 539927Notes

Reaction equation

HRID 539927 reaction equation
C([SiH](CC)CC)C.[F:8][C:9]1[C:10]([NH:44][CH:45]2[CH:51]3[CH2:52][CH2:53][CH:47]([CH2:48][CH2:49][CH2:50]3)[CH:46]2[C:54]([O:56][CH3:57])=[O:55])=[N:11][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([F:24])[CH:22]=3)[N:17](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:16]=2)=[N:13][CH:14]=1.FC(F)(F)C(O)=O>ClCCl>[F:8][C:9]1[C:10]([NH:44][CH:45]2[CH:51]3[CH2:52][CH2:53][CH:47]([CH2:48][CH2:49][CH2:50]3)[CH:46]2[C:54]([O:56][CH3:57])=[O:55])=[N:11][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([F:24])[CH:22]=3)[NH:17][N:16]=2)=[N:13][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 89914577HCID 89914577, compound

Product 1

HCID 178496844HCID 178496844, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylsilane (0.434 mL, 2.721 mmol) was added to a stirred solution of racemic methyl 7-(5-fluoro-2-(5-fluoro-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)pyrimidin-4-ylamino)bicyclo[3.2.2]nonane-6-carboxylate, 58, (0.365 g, 0.544 mmol) and trifluoroacetic acid (0.419 mL, 5.440 mmol) in dichloromethane (20 mL). The resulting yellow solution was stirred at room temperature for 2 hr and concentrated in vacuo. Water (10 mL) and aqueous saturated NaHCO3 (5 mL) were added and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organic phases were dried (MgSO4), filtered and the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography (10-90% MeOH/CH2Cl2 gradient) to afford 178 mg of the desired product as a white foamy solid: 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 8.55 (s, 1H), 8.31 (s, 1H), 5.20 (s, 1H), 3.71 (s, 3H), 2.62 (m, 1H), 2.53 (m, 1H), 2.24 (m, 1H), 2.06 (m, 1H), 1.98-1.58 (m, 9H); LC/MS Gradient 10-90%, 0.1% formic 5 min, C18/ACN, RT=2.74 minutes (M+H) 329.86.

Workup

  1. concentrationconcentrated in vacuo
  2. additionWater (10 mL) and aqueous saturated NaHCO3 (5 mL) were added
  3. extractionthe aqueous layer was extracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe crude product was purified by silica gel chromatography (10-90% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-1a2fc8c391194f9bb35cc6b98cb62c29
Source dataset
uspto-grants-2014_10
Patent number
US08871774B2

Reaction notes

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