Acetic Anhydride → HCID 68288808, compound

HRID 541195Notes

Reaction equation

HRID 541195 reaction equation
[CH3:1][C:2]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[NH:33][C:28]3[CH2:29][NH:30][CH2:31][CH2:32][C:27]=3[N:26]=2)=[CH:20][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[CH3:34][C:35](OC(C)=O)=[O:36]>CN(C=O)C.C(OCC)(=O)C>[C:35]([N:30]1[CH2:31][CH2:32][C:27]2[N:26]=[C:25]([C:21]3[C:22]([CH3:24])=[CH:23][C:2]([CH3:1])=[C:3]([CH:20]=3)[C:4]([N:6]3[CH2:7][CH2:8][CH:9]([C:12]4[CH:13]=[CH:14][C:15]([C:16]#[N:17])=[CH:18][CH:19]=4)[CH2:10][CH2:11]3)=[O:5])[NH:33][C:28]=2[CH2:29]1)(=[O:36])[CH3:34]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 68288226HCID 68288226, compound2×

Product 1

HCID 68288808HCID 68288808, compoundYield 57.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
1.5 °C

Procedure

To a stirred mixture of 4-(1-(2,4-dimethyl-5-(4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl)piperidin-4-yl)benzonitrile (compound 2.9, 20 mg, 0.02 mmol, 1.00 equiv, 50%) in DMF (2 mL) under nitrogen was added a solution of Ac2O (2.4 mg, 0.02 mmol, 1.00 equiv) in DMF (0.2 mL) dropwise at 0° C. The resulting solution was stirred for 1 h at 0-3° C. in a water/ice bath. The reaction mixture was then diluted with 50 mL of ethyl acetate and washed with 2×20 mL of brine. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The crude residue (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters)): Column, abridge C18; mobile phase, WATER WITH 0.05% NH3.H2O and CH3CN (hold 5% CH3CN in 2 min, up to 20%-46% in 10 min, up to 100% in 12 min, down to 20% in 14 min); Detector, UV 254/220 nm. The fractions containing pure compound were combined and lyophilized to yield 5.5 mg of the title compound as a white solid. m/z (ES+) 482 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 7.69 (d, J=8.1 Hz, 2H), 7.48 (d, J=8.1 Hz, 2H), 7.39-7.28 (m, 2H), 4.90 (m, 1H, partially obscured by the solvent peak), 4.67 and 4.62 (2 singlets, acetamide rotamers, MeCONCH2-imidazole, 2H), 3.92 (m, 2H), 3.66 (m, 1H), 3.23 (m, 1H), 3.00 (m, 2H), 2.85-2.76 (m, 2H), 2.48 (s, 3H), 2.41 and 2.31 (2 singlets, aryl amide rotamers, ArCH3, 3H), 2.25 and 2.22 (2 singlets, acetamide rotamers, CH3CON, 3H), 2.04 (m, 1H), 1.92-1.20 (m, 3H).

Workup

  1. washwashed with 2×20 mL of brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue (50 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-006(Waters))
  5. customin 2 min
  6. waitup to 20%-46% in 10 min
  7. waitup to 100% in 12 min
  8. waitdown to 20% in 14 min)
  9. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-dcce23d3b98d45fcbb149c2fa6fb8cb2
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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