Nitrogen → N-(2-((4-acetyloxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(m-tolyl)oxazole-4-carboxamide

HRID 527235Notes

Reaction equation

HRID 527235 reaction equation
N#N.[CH3:3][C:4]1[O:5][C:6]([C:12]2[CH:13]=[C:14]([CH3:18])[CH:15]=[CH:16][CH:17]=2)=[C:7]([C:9]([OH:11])=O)[N:8]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH2:30][C:31]1[CH:35]=[N:34][N:33]([CH2:36][C:37]2[O:38][CH:39]=[C:40]([C:42](=[O:44])[CH3:43])[N:41]=2)[N:32]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.C(Cl)Cl.O>[C:42]([C:40]1[N:41]=[C:37]([CH2:36][N:33]2[N:32]=[C:31]([NH:30][C:9]([C:7]3[N:8]=[C:4]([CH3:3])[O:5][C:6]=3[C:12]3[CH:13]=[C:14]([CH3:18])[CH:15]=[CH:16][CH:17]=3)=[O:11])[CH:35]=[N:34]2)[O:38][CH:39]=1)(=[O:44])[CH3:43]

Participants

10

Reactant 6

HCID 947NitrogenHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 669292052-Methyl-5-(m-tolyl)oxazole-4-carboxylic acidHCID 673655881-(2-((4-amino-2H-1,2,3-triazol-2-yl)methyl)oxazol-4-yl)ethanone

Product 1

HCID 67967926N-(2-((4-acetyloxazol-2-yl)methyl)-2H-1,2,3-triazol-4-yl)-2-methyl-5-(m-tolyl)oxazole-4-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-methyl-5-(m-tolyl)oxazole-4-carboxylic acid (WO 2009/077990) (1.38 g, 6.33 mmol) in dry toluene (63 mL) was treated with DMF (0.02 mL, 0.3 mmol) followed by oxalyl chloride (0.84 mL, 9.50 mmol) and the reaction mixture was stirred at rt for 50 min. The solvent was then removed under reduced pressure. The resulting acid chloride was dissolved in CH2Cl2 (23 mL) and added dropwise to a solution of 1-(2-((4-amino-2H-1,2,3-triazol-2-yl)methyl)oxazol-4-yl)ethanone (WO 2009/077990) (1.31 g, 6.33 mmol) and DIPEA (3.3 mL, 18.99 mmol) in CH2Cl2 (40 mL) and the resulting mixture was stirred at rt overnight. Water was added, the layers were separated, and the aq. layer was extracted three times with CH2Cl2. The combined org. layers were washed with brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (4:6 hept-EA) gave the title compound which was re-crystallized from hot EtOH to give a white solid: TLC: rf (4:6 hept-EA)=0.35. LC-MS-conditions 02: tR=0.99 min, [M+H]+=407.22.

Workup

  1. customThe solvent was then removed under reduced pressure
  2. dissolutionThe resulting acid chloride was dissolved in CH2Cl2 (23 mL)
  3. stirringthe resulting mixture was stirred at rt overnight
  4. customthe layers were separated
  5. extractionthe aq. layer was extracted three times with CH2Cl2
  6. washlayers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure
  10. customPurification of the residue by FC (4:6 hept-EA)

Sources & evidence

ORD record
ord-431459cb26394d1ca41570e8b43e82d5
Source dataset
uspto-grants-2016_05
Patent number
US09346793B2

Reaction notes

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