2-Methoxyphenylacetic acid → 2-(2-methoxyphenyl)-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamide

HRID 888262Notes

Reaction equation

HRID 888262 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:42][C:43]([OH:45])=O.[F:46][C:47]([F:68])([F:67])[C:48]1[CH:49]=[C:50]([S:54]([CH2:57][CH2:58][S:59][C:60]2[C:65]([NH2:66])=[CH:64][CH:63]=[CH:62][N:61]=2)(=[O:56])=[O:55])[CH:51]=[CH:52][CH:53]=1>C(Cl)Cl.CCCCCC>[CH3:34][O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:42][C:43]([NH:66][C:65]1[C:60]([S:59][CH2:58][CH2:57][S:54]([C:50]2[CH:51]=[CH:52][CH:53]=[C:48]([C:47]([F:67])([F:68])[F:46])[CH:49]=2)(=[O:56])=[O:55])=[N:61][CH:62]=[CH:63][CH:64]=1)=[O:45]

Participants

7

Reactant 4

HCID 71342-Methoxyphenylacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67133713[2-[2-[[3-(Trifluoromethyl)phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]amine

Product 1

HCID 469174342-(2-methoxyphenyl)-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamideYield 81%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

1.7 g (4.0 mmol) HATU and 1.36 ml (8.0 mmol) DIPEA were added to a solution of 582 mg (3.5 mmol) 2-(2-methoxyphenyl)acetic acid in DCM (10 ml) and the mixture was cooled to 0° C. After stirring for 15 min a solution of 725 mg (2.0 mmol) [2-[2-[[3-(trifluoromethyl)phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]amine (VPF-001) in DCM (6 ml) was added at 0° C. The mixture was then stirred for 16 h at room temperature. Then it was diluted with DCM and washed successively with a saturated aqueous NH4Cl solution, a saturated aqueous NaHCO3 solution and brine. The organic phase was dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 7:3) of the residue yielded 827 mg (1.6 mmol, 81%) 2-(2-methoxyphenyl)-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamide. MS: m/z 511.1 [M+H]+.

Workup

  1. additionwas added at 0° C
  2. washwashed successively with a saturated aqueous NH4Cl solution
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to small volume under vacuum

Sources & evidence

ORD record
ord-016d65e1ac3c42759c453fa7af7cea95
Source dataset
uspto-grants-2012_08
Patent number
US08247573B2

Reaction notes

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