1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(1,1-dioxothietan-3-yl)-2-methyl-benzamide

HRID 1770647Notes

Reaction equation

HRID 1770647 reaction equation
Cl.[O:2]=[S:3]1(=[O:8])[CH2:6][CH:5]([NH2:7])[CH2:4]1.OC1C=CC2NN=NC=2N=1.C(N=C=NCCCN(C)C)C.[Cl:30][C:31]1[CH:32]=[C:33]([C@@:39]2([C:54]([F:57])([F:56])[F:55])[O:43][N:42]=[C:41]([C:44]3[CH:52]=[CH:51][C:47]([C:48](O)=[O:49])=[C:46]([CH3:53])[CH:45]=3)[CH2:40]2)[CH:34]=[C:35]([Cl:38])[C:36]=1[F:37]>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[Cl:30][C:31]1[CH:32]=[C:33]([C@@:39]2([C:54]([F:56])([F:57])[F:55])[O:43][N:42]=[C:41]([C:44]3[CH:52]=[CH:51][C:47]([C:48]([NH:7][CH:5]4[CH2:6][S:3](=[O:8])(=[O:2])[CH2:4]4)=[O:49])=[C:46]([CH3:53])[CH:45]=3)[CH2:40]2)[CH:34]=[C:35]([Cl:38])[C:36]=1[F:37]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 717577213-Aminothietane 1,1-dioxide hclHCID 867270224-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acidHCID 178515788HCID 178515788, compound

Product 1

HCID 715293074-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-(1,1-dioxothietan-3-yl)-2-methyl-benzamideYield 62.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 100 mL vessel was charged with 1,1-dioxothietan-3-amine hydrochloride (1.2 g) in 25 mL of N,N-dimethylformamide followed by successive addition of triethylamine (2.1 mL), hydroxyazabenzotriazole (1 g), 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.4 g) and 4-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid (2.6 g) dissolved in N,N-dimethylformamide (5 mL). The mixture was then stirred overnight at room temperature. The reaction mixture was diluted in 600 mL of ethyl acetate, washed 3-times with 500 mL of brine, then with 0.5N HCl cold, dried over MgSO4 and evaporated to yield 4.6 g of the crude title compound. The product was purified over a silica gel column (eluent: CH2Cl2/EtOAc) to yield 2 g of the title compound.

Workup

  1. washwashed 3-times with 500 mL of brine
  2. dry with materialwith 0.5N HCl cold, dried over MgSO4
  3. customevaporated
  4. customto yield 4.6 g of the crude title compound
  5. customThe product was purified over a silica gel column (eluent: CH2Cl2/EtOAc)

Sources & evidence

ORD record
ord-6ffddbcb1c904ad1b478490b551ba233
Source dataset
uspto-grants-2016_02
Patent number
US09247740B2

Reaction notes

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