Pyridine → HCID 11582181, compound

HRID 969858Notes

Reaction equation

HRID 969858 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2.[C:28](OC(=O)C)(=[O:30])[CH3:29].N1C=CC=CC=1>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:30])[CH3:29])=[CH:25][CH:26]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2

Participants

7

Reactant 3

HCID 1049Pyridine2×HCID 7918Acetic Anhydride2×HCID 11552277HCID 11552277, compound

Product 1

HCID 11582181HCID 11582181, compoundYield 45.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-aminophenyl)benzoxazole-4-carboxamide (22 mg, 0.06 mmol) in dichloromethane was added acetic anhydride (10 μL, 0.12 mmol), pyridine (15 μL, 0.18 mmol) and DMAP (1.5 mg, 0.01 mmol). The reaction mixture was stirred at room temperature for 3 h. Acetic anhydride (2 equiv) and pyridine (3 equiv) were re-filled and the reaction was stirred at room temperature for an additional 1.5 h. The mixture was diluted with ethyl acetate (20 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×50 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) and then recrystallized from acetonitrile to afford N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-acetylaminophenyl)benzoxazole-4-carboxamide (11 mg, 44%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.59-9.58 (m, 1H), 8.17-8.16 (m, 3H), 7.77-7.69 (m, 4H), 7.46-7.43 (m, 1H), 7.39 (t, J=8.0 Hz, 1H), 4.40-4.33 (m, 1H), 2.26 (s, 3H), 3.58-3.53 (m, 1H), 3.19-2.88 (m, 3H), 2.13-1.70 (m, 6H); MS (ESI+) m/z 405 (M+H); HPLC 97.3% (AUC), tR=13.85 min.

Workup

  1. stirringthe reaction was stirred at room temperature for an additional 1.5 h
  2. washwashed with a saturated solution of sodium bicarbonate
  3. extractionThe aqueous layer was further extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)
  8. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-eed30f7f258144d8b42aa4a1fe9d6e4e
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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