Trifluoroacetic acid methylene chloride → HCID 56848564, compound

HRID 473142Notes

Reaction equation

HRID 473142 reaction equation
[F:1][C:2]([F:36])([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][N:30]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[N:16](C(OC(C)(C)C)=O)[N:15]=2)[C:10]2[C:5](=[CH:6][C:7]([O:27][CH3:28])=[CH:8][CH:9]=2)[N:4]=1.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[F:36][C:2]([F:1])([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][N:30]=1)[C:3]1[N:12]=[C:11]([NH:13][C:14]2[CH:18]=[C:17]([CH3:19])[NH:16][N:15]=2)[C:10]2[C:5](=[CH:6][C:7]([O:27][CH3:28])=[CH:8][CH:9]=2)[N:4]=1

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 66614853HCID 66614853, compound

Product 1

HCID 56848564HCID 56848564, compoundYield 41.2%

Procedure

To tert-Butyl 3-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4-ylamino)-5-methyl-1H-pyrazole-1-carboxylate (100 mg, 0.20 mmol) was added 20% TFA/DCM, and the mixture was stirred at rt for 2.5 h. The mixture was concentrated and the residue was purified by preparative reverse-phase HPLC (TFA as a modifier). The fractions containing the desired product were neutralized with saturated aq NaHCO3 and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxy-N-(5-methyl-1H-pyrazol-3-yl)quinazolin-4-amine as an off-white solid (33 mg, 41%). 1H NMR (250 MHz, DMSO-d6) δ 12.10 (s, 1H), 10.54 (s, 1H), 8.67 (d, J=2.0 Hz, 1H), 8.59 (d, J=8.16 Hz, 1H), 7.97-8.06 (m, 2H), 7.22-7.28 (m, 2H), 5.97 (s, 1H), 3.93 (s, 3H), 2.17 (s, 3H). LCMS (ESI) m/z 401 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by preparative reverse-phase HPLC (TFA as a modifier)
  3. additionThe fractions containing the desired product
  4. extractionextracted with EtOAc (100 mL)
  5. customThe organic layer was separated
  6. washwashed with brine (2×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-abb9d8d2e2f041938b0ebe557594a078
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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