Trifluoroacetic acid → HCID 59252409, compound

HRID 42291Notes

Reaction equation

HRID 42291 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][N:21](C(OC(C)(C)C)=O)[CH2:20][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][NH:21][CH2:20][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 178451799HCID 178451799, compound

Product 1

HCID 59252409HCID 59252409, compoundYield 20.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Solid tert-butyl 4-(4-(2-phenylpyrimidin-5-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (Example 17, 122 mg, 0.30 mmol) was treated with trifluoroacetic acid 2.0 mL) at room temperature for 15 minutes. Three times the reaction mixture was diluted with toluene and concentrated under reduced pressure to provide a dark semi-solid. The crude material was chromatographed on silica (12 g) eluted with 1:5:85 v/v acetic acid-methanol-dichloromethane. Some clean fractions were collected, concentrated, and the purified material was three times diluted with toluene and concentrated then promoted to solidify under hexane with scratching to afford the title compound (19 mg) as a light-pink acetate salt. The remaining fractions were collected, concentrated, three times diluted with toluene and concentrated to afford a semi-solid; Rf 0.17 with 1/10/90 v/v acetic acid/methanol/dichloromethane; 1H-NMR (400 MHz; DMSO-d6) δ 9.20 (s, 2H), 8.6-8.8 (br d, 1H), 8.3-8.5 (m, 3H), 7.83 (s, 1H), 7.45-7.55 (m, 3H), 3.2-3.5 (m, 2H), 2.95-3.2 (m, 3H), 2.1-2.2 (m, 2H), 1.8-2.0 (m, 5H); MS (ESI+) m/z 306 (M+1); H-PGDS FPBA IC50: 1 μM.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto provide a dark semi-solid
  3. customThe crude material was chromatographed on silica (12 g)
  4. washeluted with 1:5:85 v/v acetic acid-methanol-dichloromethane
  5. customSome clean fractions were collected
  6. concentrationconcentrated
  7. additiondiluted with toluene
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-58fea4b0bd8e471aae782d869fcf4ede
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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