Trifluoroacetic acid → HCID 178474525, compound

HRID 2241322Notes

Reaction equation

HRID 2241322 reaction equation
[CH2:1]([N:8]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]3[N:25](CC4C=CC(OC)=CC=4)[N:26]=[C:27]([CH3:28])[C:20]=23)=[C:14]([F:38])[CH:13]=1)[C:9](=[O:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>>[CH2:1]([N:8]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]3[NH:25][N:26]=[C:27]([CH3:28])[C:20]=23)=[C:14]([F:38])[CH:13]=1)[C:9](=[O:11])[CH3:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68516494HCID 68516494, compound

Product 1

HCID 178474525HCID 178474525, compoundYield 59%

Conditions

Temperature
50 °C

Procedure

To a flask containing N-benzyl-N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)acetamide (38 mg, 0.074 mmol) at ambient temperature under a drying tube was added TFA (2 mL). The mixture was heated to 50° C. and stirred for 4 hours. The reaction was cooled to ambient temperature and concentrated. The residue was treated with 5 mL 10% sodium carbonate and then 5 mL dichloromethane. The mixture was rapidly stirred and the layers separated. The aqueous phase was extracted with dichloromethane and the combined organic layers were dried (MgSO4), filtered, and concentrated. The crude material was loaded onto a Biotage 12S column with dichloromethane and eluted with 7/3 EtOAc/hexanes to provide the desired product as a white foam (17 mg, 59% yield). 1H NMR (400 MHz, CDCl3) δ 11.68 (br s, 1H), 8.35 (m, 1H), 7.31 (m, 3H), 7.23 (m, 3H), 6.93 (m, 2H), 6.16 (d, 1H), 4.93 (s, 2H), 2.73 (s, 3H), 2.00 (br s, 3H). LCMS (APCI+): m/z 391 (M+1) detected.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. concentrationconcentrated
  3. additionThe residue was treated with 5 mL 10% sodium carbonate
  4. stirringThe mixture was rapidly stirred
  5. customthe layers separated
  6. extractionThe aqueous phase was extracted with dichloromethane
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluted with 7/3 EtOAc/hexanes

Sources & evidence

ORD record
ord-f6480f82c38b422aa6b5129d24f9a175
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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