Trifluoroacetic acid → HCID 89630059, compound

HRID 882183Notes

Reaction equation

HRID 882183 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[C:14]2[C:13]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:26])[C:23]([CH3:25])=[CH2:24])[CH:18]=[CH:19][CH:20]=3)=[N:12][CH:11]=[N:10][C:9]=2[N:8](COCC[Si](C)(C)C)[CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO.CCOC(C)=O>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[C:14]2[C:13]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:26])[C:23]([CH3:25])=[CH2:24])[CH:18]=[CH:19][CH:20]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89630044HCID 89630044, compound

Product 1

HCID 89630059HCID 89630059, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude N-(3-(5-(thiazol-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide (38 mg, 0.076 mmol) in DCM (1.0 mL), was added TFA (1.0 mL). The resulting solution was stirred at room temperature for approximately 3 hours before being concentrated in vacuo. The crude residue was then taken up into MeOH (1.0 mL) and ammonium hydroxide (1.0 mL) was added, and the resulting mixture was stirred at room temperature for approximately 30 minutes. The reaction was concentrated to afford a crude solid that was dissolved in a mixture of MeOH and EtOAc, filtered through 2 Stratospheres™ PL-HCO3 MP SPE cartridges, concentrated in vacuo and purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Lyophyllization of the desired fractions afforded N-(3-(5-(thiazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide as an off-white solid. LRMS (ESI) calcd for C19H15N5OS [M+H]+: 362, found 362. 1H NMR (600 MHz, DMSO-d6) δ 12.93 (s, 1H), 9.75 (s, 1H), 8.92 (s, 1H), 8.10 (d, J=2.4 Hz, 1H), 7.91 (s, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.55 (m, 2H), 7.07 (t, J=7.8 Hz, 1H), 6.91 (d, J=7.8 Hz, 1H), 5.74 (s, 1H), 5.47 (s, 1H), 1.90 (s, 3H).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature for approximately 30 minutes
  4. concentrationThe reaction was concentrated
  5. customto afford a crude solid
  6. filtrationfiltered through 2 Stratospheres™ PL-HCO3 MP SPE cartridges
  7. concentrationconcentrated in vacuo
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-7af0f5614b3f4fb4ad646cdb796ede1d
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

Loading…