Benzoyl chloride → 3-benzamido-4-cyano-2,5-difluoro-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide

HRID 1943124Notes

Reaction equation

HRID 1943124 reaction equation
[NH2:1][C:2]1[C:3]([F:32])=[C:4]([CH:26]=[C:27]([F:31])[C:28]=1[C:29]#[N:30])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([C:15]([F:24])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])=[CH:10][C:9]=1[CH3:25])=[O:6].N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[C:55](Cl)(=[O:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>C(Cl)(Cl)Cl>[C:55]([NH:1][C:2]1[C:3]([F:32])=[C:4]([CH:26]=[C:27]([F:31])[C:28]=1[C:29]#[N:30])[C:5]([NH:7][C:8]1[C:13]([CH3:14])=[CH:12][C:11]([C:15]([F:24])([C:16]([F:18])([F:19])[F:17])[C:20]([F:21])([F:22])[F:23])=[CH:10][C:9]=1[CH3:25])=[O:6])(=[O:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chloride2×HCID 592269483-amino-4-cyano-2,5-difluoro-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamideHCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 592269513-benzamido-4-cyano-2,5-difluoro-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamideYield 15%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 3-amino-4-cyano-2,5-difluoro-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide (70 mg, 0.15 mmol) (Example I16) in chloroform (0.75 ml) were added 1,8-diazabicycloundec-7-ene (“DBU”) (49 μl, 0.33 mmol) and benzoyl chloride (17 μl, 0.15 mmol). The reaction mixture was heated in a microwave to 140° C. for 30 minutes. Two further portions of benzoyl chloride (17 μl, 0.15 mmol) were added and heating continued at 140° C. for 30 minutes each time. The reaction mixture was partitioned between water and chloroform. The aqueous phase was extracted twice with chloroform. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase chromatography (eluent:trifluoroacetic acid/water/acetonitrile 1:4:5 to 1:1:8) to give Compound No. E36 of Table E (0.013 g, 15% yield) as an off-white solid. M.p. 245-248° C. 1H-NMR (400 MHz, CDCl3): 2.28 (6H, s), 7.38 (2H, s), 7.15-8.1 (8H, m) ppm.

Workup

  1. temperatureheating
  2. customThe reaction mixture was partitioned between water and chloroform
  3. extractionThe aqueous phase was extracted twice with chloroform
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase chromatography (eluent:trifluoroacetic acid/water/acetonitrile 1:4:5 to 1:1:8)
  7. customto give Compound No

Sources & evidence

ORD record
ord-457b83b6bddc4f8fbc2855bb3509c325
Source dataset
uspto-grants-2013_03
Patent number
US08389766B2

Reaction notes

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