Acetic Anhydride → HCID 178467166, compound

HRID 1371127Notes

Reaction equation

HRID 1371127 reaction equation
Cl.[CH3:2][CH:3]1[CH2:8][CH:7]([C:9]2[NH:14][C:13]3=[CH:15][CH:16]=[N:17][C:12]3=[CH:11][N:10]=2)[CH2:6][CH:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[NH:4]1.[C:24](OC(=O)C)(=[O:26])[CH3:25].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:24]([C:15]1[CH:16]=[N:17][C:12]2[C:13]=1[NH:14][C:9]([CH:7]1[CH2:6][CH:5]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[NH:4][CH:3]([CH3:2])[CH2:8]1)=[N:10][CH:11]=2)(=[O:26])[CH3:25]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 11430Potassium CarbonateHCID 178423311HCID 178423311, compound

Product 1

HCID 178467166HCID 178467166, compoundYield 22.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-methyl-6-phenyl-4-piperidylpyrrolo[3,2-d]pyridine (Example 35) (50 mg, 0.17 mmol), acetic anhydride (Aldrich Chemical Company) (168 mg, 1.64 mmol, 9.7 eq), K2CO3 (227 mg, 1.64 mmol, 9.7 eq) and 4-N,N-dimethylaminopyridine (2.6 mg, 0.021 mmol, 0.12 eq) in anhydrous DMF (2.0 mL) was stirred under N2 at 110° C. overnight. After cooling to the room temperature, the reaction was quenched by the addition of saturated NaHCO, (5 mL) and extracted with CHCl3 (3×30 mL). The organic layers were washed with saturated NaCl, dried over Na2SO4 and concentrated with a rotary evaporator. The crude material was purified by flash chromatography on silica gel with a gradient eluant of EtOAc(0-25%):hexanes(100-75%) to afford 13 mg (22%) of the title compound as an off-white solid. Mp: 188-190° C. 1H NMR (CDCl3; 400 MHz): δ 11.43 (s, 1), 7.61 (d, 2, J=7.4), 7.43 (t, 2, J=7.4), 7.37 (t, 1, J=7.4), 4.88 (br s, 2), 4.06 (br s, 2), 2.58 (s, 3), 2.11 (s, 3), 1.73 (br s, 6). MS m/z: 335 (M+1), 333 (M−1). HRMS (NBA-NaI) m/z Calcd for M+H, C20H22N4O: 335.1888. Found: 335.1872.

Workup

  1. temperatureAfter cooling to the room temperature
  2. customthe reaction was quenched by the addition of saturated NaHCO, (5 mL)
  3. extractionextracted with CHCl3 (3×30 mL)
  4. washThe organic layers were washed with saturated NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated with a rotary evaporator
  7. customThe crude material was purified by flash chromatography on silica gel with a gradient eluant of EtOAc(0-25%)

Sources & evidence

ORD record
ord-35f3d6f4c9d4405e8fb46d716e58a548
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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