Dimethylformamide → N-[3-(2-methylimidazol-1-yl)propyl]-2-phenylbenzoxazole-4-carboxamide

HRID 969804Notes

Reaction equation

HRID 969804 reaction equation
[C:1]1([C:7]2[O:8][C:9]3[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.C(=O)(O)[O-].[Na+].[CH3:35][C:36]1[N:37]([CH2:41][CH2:42][CH2:43][NH2:44])[CH:38]=[CH:39][N:40]=1>C(Cl)Cl>[CH3:35][C:36]1[N:37]([CH2:41][CH2:42][CH2:43][NH:44][C:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:11][C:10]=23)=[O:18])[CH:38]=[CH:39][N:40]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 31521053-(2-methyl-1H-imidazol-1-yl)propan-1-amineHCID 108683692-Phenylbenzoxazole-4-carboxylic acid

Product 1

HCID 11674911N-[3-(2-methylimidazol-1-yl)propyl]-2-phenylbenzoxazole-4-carboxamideYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A 100-mL one-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 2-phenylbenzoxazole-4-carboxylic acid (0.190 g, 0.79 mmol), DMF (0.588 g, 8.00 mmol) and anhydrous methylene chloride (15 mL). The resulting solution was treated with oxalyl chloride (1.46 g, 11.5 mmol) dropwise over 5 min and stirred at ambient temperature under nitrogen for 2 h. After this time, the reaction mixture was evaporated to a solid residue which was dissolved in anhydrous methylene chloride (15 mL). The resulting solution was treated with sodium bicarbonate (0.672 g, 8.00 mmol) and stirred at ambient temperature under nitrogen for 15 min. After this time, a solution of 3-(2-methylimidazol-1-yl)propylamine (0.332 g, 2.39 mmol) in anhydrous methylene chloride (5 mL) was added and the mixture stirred for a further 20 h. The reaction mixture was then diluted with methylene chloride (50 mL) and washed with 10% aqueous potassium carbonate (10 mL) followed by water (20 mL). The organic phase was dried over sodium sulfate, filtered and evaporated to a solid residue which was further purified by preparative HPLC to give 0.040 g (14% yield) of N-[3-(2-methylimidazol-1-yl)propyl]-2-phenylbenzoxazole-4-carboxamide as a white solid: mp 145-148° C.; 1H NMR (300 MHz, CD3OD) δ 8.33 (m, 2H), 8.03 (dd, J=7.8, 0.9 Hz, 1H), 7.86 (dd, J=8.2, 0.9 Hz, 1H), 7.69-7.59 (m, 4H), 7.52 (t, J=8.0 Hz, 1H), 7.38 (d, J=2.1 Hz, 1H), 4.32 (t, J=7.1 Hz, 2H), 3.67 (t, J=7.1 Hz, 2H), 2.65 (s, 3H), 2.31 (m, 2H); MS (ESI) m/z 361 [M+H]+.

Workup

  1. customA 100-mL one-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. customAfter this time, the reaction mixture was evaporated to a solid residue which
  4. dissolutionwas dissolved in anhydrous methylene chloride (15 mL)
  5. stirringstirred at ambient temperature under nitrogen for 15 min
  6. stirringthe mixture stirred for a further 20 h
  7. washwashed with 10% aqueous potassium carbonate (10 mL)
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to a solid residue which
  11. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-f1384898c5554e94bda2570f5cde7c52
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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