Triethylamine → HCID 67357288, compound

HRID 2190633Notes

Reaction equation

HRID 2190633 reaction equation
[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([OH:27])=O)=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[C:29]([Cl:34])(=O)[C:30](Cl)=O.FC1C=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][C:37]=1[NH2:38].C(N(CC)CC)C>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C=O)C>[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH:38][C:37]4[CH:39]=[C:40]([C:43]([F:46])([F:45])[F:44])[CH:41]=[CH:30][C:29]=4[Cl:34])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=[CH:11][CH:12]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1363492-Fluoro-5-(trifluoromethyl)anilineHCID 59318029HCID 59318029, compound

Product 1

HCID 67357288HCID 67357288, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a suspension of 4-[4-(4-carboxyphenyl)-piperazin-1-yl]-benzoic acid tert-butyl ester (100 mg, 0.26 mmol) in methylene chloride (5 mL) was added oxalyl chloride (2M, 0.2 mL) and a catalytic amount of DMF. The mixture was stirred for 30 minutes and solvents were evaporated. The residue was dried and then mixed with 2-fluoro-5-trifluoromethylaniline (65 mg, 0.36 mmol) and triethyl amine (56 μL, 0.38 mmol) in toluene (6 mL). The mixture was heated in a sealed tube at 140° C. for 3 hrs. Solvents were then evaporated and the residue was extracted with water and ethyl acetate. The organic layer was dried and evaporated. The residue was triturated with ethyl acetate to give the intermediate 4-{4-[4-(2-chloro-5-trifluoromethyl-phenylcarbamoyl)-phenyl]-piperazin-1-yl}-benzoic acid tert-butyl ester. This intermediate was then suspended in methylene chloride (3 mL and trifluoro acetic acid (1 mL) was added. The mixture was stirred for 1 hr and solvents were evaporated. The residue was dried and then triturated with ethyl acetate to give 4-{4-[4-(2-fluoro-5-trifluoromethyl-phenylcarbamoyl)-phenyl]-piperazin-1-yl}-benzoic acid. LCMS calc for C25H21F4N3O3 (m/e) 487, obsd 488 (M+H).

Workup

  1. customsolvents were evaporated
  2. customThe residue was dried
  3. customSolvents were then evaporated
  4. extractionthe residue was extracted with water and ethyl acetate
  5. customThe organic layer was dried
  6. customevaporated
  7. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-71e8ca13e32e4c2a8ac2746849953330
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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