Triethylamine → HCID 59185678, compound

HRID 1509870Notes

Reaction equation

HRID 1509870 reaction equation
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:25]([O:29][C:30]([N:32]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]2[CH:44]=[CH:43][C:42]([NH2:45])=[CH:41][CH:40]=2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[C:25]([O:29][C:30]([N:32]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]2[CH:44]=[CH:43][C:42]([NH:45][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:41][CH:40]=2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 18008968Tert-butyl 4-(4-aminophenyl)-1,4-diazepane-1-carboxylate

Product 1

HCID 59185678HCID 59185678, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (1.0 g, 3.90 mmol), methylene chloride (50 mL), and a catalytic amount of DMF was stirred under argon, and oxalyl chloride (2M in methylene chloride, 2 mL, 4.0 mmol) was dripped into the mixture over 5 min. The mixture was stirred at room temperature for 1.0 hr and the reaction was concentrated to dryness. Benzene was added and the solution was evaporated to dryness again. The white-yellow solid was re-dissolved in methylene chloride (30 mL) and dripped, under argon, into a solution of 4-(4-amino-phenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (1.2 g, 4.0 mmol), and triethylamine (0.6 g, 5.8 mmol) in methylene chloride (50 mL). The reaction was stirred at room temperature for 0.5 hr then concentrated and the residue was taken up in EtOAc (100 mL) and washed with saturated ammonium chloride (100 mL), brine (100 mL) and dried with anhydrous sodium sulfate. The solvent was removed and the residue was purified on a flash column chromatography with EtOAc/hexanes to afford 4-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-[1,4]diazepane-1-carboxylic acid tert-butyl ester (1.65 g, 83% yield) as a white solid. ES-MS for C27H29F3N4O4 calcd. (m/e) 530, observed 531 (M+H).

Workup

  1. concentrationthe reaction was concentrated to dryness
  2. additionBenzene was added
  3. customthe solution was evaporated to dryness again
  4. dissolutionThe white-yellow solid was re-dissolved in methylene chloride (30 mL)
  5. stirringThe reaction was stirred at room temperature for 0.5 hr
  6. concentrationthen concentrated
  7. washwashed with saturated ammonium chloride (100 mL), brine (100 mL)
  8. dry with materialdried with anhydrous sodium sulfate
  9. customThe solvent was removed
  10. customthe residue was purified on a flash column chromatography with EtOAc/hexanes

Sources & evidence

ORD record
ord-1803693df2594b9fa8ad7989aa97405e
Source dataset
uspto-grants-2012_07
Patent number
US08211884B2

Reaction notes

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