Diisopropylethylamine → N-(1-{4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-1H-[1,2,3]triazol-4-ylmethyl)-isonicotinamide

HRID 388378Notes

Reaction equation

HRID 388378 reaction equation
[N:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[CH2:18][C:17]([C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=3)([C:19]([F:22])([F:21])[F:20])[O:16][N:15]=2)=[CH:6][CH:5]=1)=[N+:2]=[N-:3].CCN(C(C)C)C(C)C.[CH2:40]([NH:43][C:44](=[O:51])[C:45]1[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=1)[C:41]#[CH:42]>CN(C=O)C.[Cu]I>[Cl:29][C:27]1[CH:28]=[C:23]([C:17]2([C:19]([F:22])([F:20])[F:21])[O:16][N:15]=[C:14]([C:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:4]([N:1]4[CH:42]=[C:41]([CH2:40][NH:43][C:44](=[O:51])[C:45]5[CH:46]=[CH:47][N:48]=[CH:49][CH:50]=5)[N:3]=[N:2]4)=[CH:5][CH:6]=3)[CH2:18]2)[CH:24]=[C:25]([Cl:30])[CH:26]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 18451411N-prop-2-ynyl-isonicotinamideHCID 866581613-(4-Azido-naphthalen-1-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

Product 1

HCID 46842400N-(1-{4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-1H-[1,2,3]triazol-4-ylmethyl)-isonicotinamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

CuI (211 mg) is added to a solution of 3-(4-azido-naphthalen-1-yl)-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole (500 mg), DIPEA (3.3 ml) and N-prop-2-ynyl-isonicotinamide (180 mg) in DMF (2.0 ml). After 5 hours at room temperature, the reaction is quenched with a saturated solution of NaHCO3 and extracted with dichloromethane. The combined organic phases are dried over Na2SO4 and concentrated in mow. The crude product is purified on a semi-preparative HPLC to yield N-(1-{4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-naphthalen-1-yl}-1H-[1,2,3]triazol-4-ylmethyl)-isonicotinamide as a colorless oil.

Workup

  1. customthe reaction is quenched with a saturated solution of NaHCO3
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic phases are dried over Na2SO4
  4. concentrationconcentrated in mow
  5. customThe crude product is purified on a semi-preparative HPLC

Sources & evidence

ORD record
ord-04ec5f95e47e4ce2b47aaa19d48a643b
Source dataset
uspto-grants-2013_02
Patent number
US08377942B2

Reaction notes

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