Pyridine → HCID 44176494, compound

HRID 1673044Notes

Reaction equation

HRID 1673044 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[C:20]([C@H:22]4[CH2:26][CH2:25][CH2:24][NH:23]4)[N:19]=[C:18]3[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]([F:36])([F:35])[F:34])=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].N1C=CC=CC=1.[C:43](Cl)(=[O:45])[CH3:44]>C1COCC1>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:21]=[C:20]([C@H:22]4[CH2:26][CH2:25][CH2:24][N:23]4[C:43](=[O:45])[CH3:44])[N:19]=[C:18]3[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:33]([F:36])([F:34])[F:35])=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 44178155HCID 44178155, compound

Product 1

HCID 44176494HCID 44176494, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into an 8 mL vial was weighed 26.8 mg (52 μmol) of 1-(3′-(methylsulfonyl)biphenyl-4-yl)-4-((R)-pyrrolidin-2-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole. The vial was charged with 0.5 mL of THF, followed by 15 μL (185 μmol) of pyridine, and 7 μL (98 μmol) of acetyl chloride. After stirring for 30 minutes at ambient temperature, LC/MS analysis of the reaction showed complete conversion to product. The reaction was quenched by addition of a small amount of water. The reaction solution was directly injected into the reverse phase preparative HPLC and eluted with acetonitrile/water. (Phenomenex Axia Gemini C18 30×100 mm 5 μm, A=H2O with 0.1% trifluoroacetic acid, B=acetonitrile with 0.1% trifluoroacetic acid, 17 minute gradient from 10% B to 100% B at 35 mL/minute). Product fractions were combined, made basic by the addition of sat. NaHCO3, and concentrated in vacuo to remove the acetonitrile. The resulting basic aqueous was extracted with CH2Cl2 (3×), and the organics were dried over Na2SO4, filtered and concentrated in vacuo. The resulting 1-((2R)-2-(1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazol-4-yl)pyrrolidin-1-yl)ethanone was isolated as a white powder, yield 20.2 mg (70%); 1H NMR (400 MHz, CDCl3): δ 8.10-8.07 (m, 1H), 7.95-7.90 (m, 1H), 7.83-7.79 (m, 1H), 7.77-7.72 (m, 1H), 7.67-7.61 (m, 1H), 7.56-7.42 (m, 4H), 7.38-7.34 (m, 0.6H), 7.30-7.26 (m, 0.4H), 7.20-7.16 (m, 2.4H), 7.05-7.04 (m, 0.6H), 5.34-5.31 (m, 0.4H), 5.08-5.05 (m, 0.6H), 3.78-3.67 (m, 1H), 3.63-3.49 (m, 1H), 3.09 (s, 1.8H), 3.08 (s, 1.2H), 2.52-2.46 (m, 0.4H), 2.36-2.26 (m, 1.6H), 2.14 (s, 1.8H), 2.12 (s, 1.2H), 2.08-1.95 (m, 2H); MS (ES): 554.3 [M+H]+.

Workup

  1. customThe reaction was quenched by addition of a small amount of water
  2. washeluted with acetonitrile/water
  3. customwith 0.1% trifluoroacetic acid, 17 minute gradient
  4. additionmade basic by the addition of sat. NaHCO3
  5. concentrationconcentrated in vacuo
  6. customto remove the acetonitrile
  7. extractionThe resulting basic aqueous was extracted with CH2Cl2 (3×)
  8. dry with materialthe organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8f2e4f4531ce4f43a8c61531253d6d51
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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