Trifluoroacetic acid → HCID 59252397, compound

HRID 42294Notes

Reaction equation

HRID 42294 reaction equation
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([CH:18]4[CH2:23][CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]4)[NH:16][CH:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[NH:14][C:15]([CH:18]4[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]4)=[N:16][CH:17]=3)=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178451854HCID 178451854, compound

Product 1

HCID 59252397HCID 59252397, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Solid (±)-tert-butyl 3-(4-(2-phenylpyrimidin-5-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (Example 21) was treated with 0.5 mL of trifluoroacetic acid at room temperature for 0.5 hour. Three times the reaction mixture was diluted with toluene and concentrated to give a dark semi-solid. The crude material was chromatographed on silica (4 g) eluted with 1:10:90 v/v acetic acid-methanol-dichloromethane. The clean fractions were collected, concentrated under reduced pressure, and the material was three times diluted with toluene and concentrated, then dried under high vacuum to afford the title compound as a pale yellow solid; Rf 0.17 with 1:10:90 v/v acetic acid-methanol-dichloromethane; melting point 140° C.; 1H-NMR (400 MHz; DMSO-d6) δ 9.22 (s, 2H), 8.5-9.2 (br s, 2H), 8.35-8,45 (m, 2H), 7.9 (d, 1H), 7.4-7.5 (m, 3H), 3.4-3.6 (m, 2H), 3.2-3.4 (m, 2H), 2.9-3.1 (m, 1H), 2.0-2.2 (m, 1H), 1.6-1.9 (m, 3H); MS (ESI+) m/z 306 (M+1); H-PGDS FPBA IC50: 1.25 μM.

Workup

  1. concentrationconcentrated
  2. customto give a dark semi-solid
  3. customThe crude material was chromatographed on silica (4 g)
  4. washeluted with 1:10:90 v/v acetic acid-methanol-dichloromethane
  5. customThe clean fractions were collected
  6. concentrationconcentrated under reduced pressure
  7. additiondiluted with toluene
  8. concentrationconcentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-bac819213b264fd59a0e0dff04929d50
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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