Trifluoroacetic acid → HCID 136247206, compound

HRID 1022450Notes

Reaction equation

HRID 1022450 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11](=[O:26])[C:12]3[CH:17]=[CH:16][N:15]([CH2:18][O:19]CC[Si](C)(C)C)[C:13]=3[N:14]=2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[OH:19][CH2:18][N:15]1[C:13]2[N:14]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:27])([F:28])[F:1])=[CH:8][CH:7]=3)[NH:10][C:11](=[O:26])[C:12]=2[CH:17]=[CH:16]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136344412HCID 136344412, compound

Product 1

HCID 136247206HCID 136247206, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(4-(trifluoromethyl)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one (47.7 mg, 116 μmol) in anhydrous methylene chloride (6.0 mL) was cooled, under nitrogen, to 0° C. The solution was then treated portion-wise with trifluoroacetic acid (1.5 mL). The reaction was stirred under nitrogen at 0° C. for 30 min. At this time, the reaction was warmed to room temperature where it continued to stir for an additional 3 h. At this time, the reaction was diluted with methylene chloride and was concentrated in vacuo onto Celite® while maintaining a water bath temperature less than or equal to 30° C. Flash chromatography (12 g silica gel column, 40-70% ethyl acetate/hexanes) afforded 7-hydroxymethyl-2-(4-trifluoromethyl-phenyl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one as an off-white solid (20.9 mg, 58.0%). 1H NMR (300 MHz, DMSO-d6) δ ppm 5.55 (d, J=7.91 Hz, 2H) 6.56 (d, J=3.39 Hz, 1H) 6.63 (t, J=7.35 Hz, 1H) 7.27 (d, J=3.39 Hz, 1H) 7.91 (d, J=8.48 Hz, 2H) 8.37 (d, J=8.10 Hz, 2H) 12.38 (s, 1H). LC-MS calcd. for C14H11F3N3O2 [(M+H)+] 310, obsd. 310.0.

Workup

  1. temperatureAt this time, the reaction was warmed to room temperature where it
  2. stirringto stir for an additional 3 h
  3. concentrationwas concentrated in vacuo onto Celite®
  4. temperaturewhile maintaining a water bath temperature less than or equal to 30° C

Sources & evidence

ORD record
ord-88288c7c2c1f4041bf03e4bbc7c96ce2
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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