Trifluoroacetate → 4-[(3R)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-N-(1,1-dioxothietan-3-yl)-2-methyl-benzamide

HRID 589646Notes

Reaction equation

HRID 589646 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]2([C:24]([F:27])([F:26])[F:25])[CH2:13][C:12]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([CH3:23])[CH:15]=3)=[N:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.FC(F)(F)C([O-])=O.[O:35]=[S:36]1(=[O:41])[CH2:39][CH:38]([NH2:40])[CH2:37]1.ON1C2C=CC=NC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]2([C:24]([F:25])([F:26])[F:27])[CH2:13][C:12]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:40][CH:38]4[CH2:39][S:36](=[O:41])(=[O:35])[CH2:37]4)=[O:20])=[C:16]([CH3:23])[CH:15]=3)=[N:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

9

Reactant 5

HCID 84468TrifluoroacetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 116798243H-1,2,3-Triazolo[4,5-b]pyridine, 1-oxideHCID 552971143-Aminothietane 1,1-dioxideHCID 710777204-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid

Product 1

HCID 547599394-[(3R)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-N-(1,1-dioxothietan-3-yl)-2-methyl-benzamideYield 35.4%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-[(3R)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-2-methyl-benzoic acid (68 mg) in dichloromethane (2.5 mL) was added triethylamine (0.05 mL) at ambient temperature. The solution was then stirred for 5 min under argon and trifluoroacetate salt of 1,1-Dioxo-llambda*6*-thietan-3-ylamine (46 mg) was added. To this solution, 1-hydroxyazabenzotriazole (25 mg) then 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (35 mg) were added. The solution was stirred at ambient temperature for 3 days. The reaction mixture was diluted with ethyl acetate and washed with water. The combined organic phases were dried over anhydrous sodium sulfate, the suspension was filtered and the solution was evaporated to give a crude residue which was purified by chromatography on silica gel (eluent: heptane/ethyl acetate, from 1:0 to 6:4) to give 4-[(3R)-3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-N-(1,1-dioxothietan-3-yl)-2-methyl-benzamide (30 mg) as a white solid.

Workup

  1. stirringThe solution was stirred at ambient temperature for 3 days
  2. washwashed with water
  3. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  4. filtrationthe suspension was filtered
  5. customthe solution was evaporated
  6. customto give a crude residue which
  7. customwas purified by chromatography on silica gel (eluent: heptane/ethyl acetate, from 1:0 to 6:4)

Sources & evidence

ORD record
ord-38a0186fd91c4770abe527e450122e39
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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