Phosgene → 4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-methyl-N-{2-[2-(5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-ethoxy]-phenyl}-benzamide

HRID 448917Notes

Reaction equation

HRID 448917 reaction equation
C([O:5][C:6]([NH:8][NH:9][C:10](=O)[CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N:20]([C:22](=[O:42])[C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([C:30]2[CH:31]=[N:32][C:33]([C:38]([F:41])([F:40])[F:39])=[CH:34][C:35]=2[C:36]#[N:37])[CH:24]=1)[CH3:21])=[O:7])(C)(C)C.CCN(C(C)C)C(C)C.C(Cl)(Cl)=O>Cl.O1CCOCC1>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C:22]([N:20]([CH3:21])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[O:13][CH2:12][CH2:11][C:10]2[O:7][C:6](=[O:5])[NH:8][N:9]=2)=[O:42])=[CH:24][C:25]=1[C:30]1[CH:31]=[N:32][C:33]([C:38]([F:41])([F:40])[F:39])=[CH:34][C:35]=1[C:36]#[N:37]

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 68602450HCID 68602450, compound

Product 1

HCID 593703564-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-methyl-N-{2-[2-(5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-ethoxy]-phenyl}-benzamideYield 48.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

N′-[3-(2-{[4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-benzoyl]-methyl-amino}-phenoxy)-propionyl]-hydrazinecarboxylic acid tert-butyl ester (40.1 mg, 0.065 mmol) was stirred in 4N HCl in dioxane (5 mL) for 2 hrs and was concentrated. The residue was suspended in toluene (5 mL) containing DIPEA (25.2 mg, 0.19 mmol). Phosgene (20% in toluene, 8.2 μL, 0.077 mmol) was added and the mixture was stirred at rt for 24 hrs. The mixture was concentrated and purified via reverse phase preparative LCMS to give 4-chloro-3-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-N-methyl-N-{2-[2-(5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-ethoxy]-phenyl}-benzamide 31-1 (17 mg). MS [M+H]+: 544.1; tR=5.11 min. (method 3)

Workup

  1. concentrationwas concentrated
  2. concentrationThe mixture was concentrated
  3. custompurified via reverse phase preparative LCMS

Sources & evidence

ORD record
ord-78c7527722d64d80af2638780c121ff0
Source dataset
uspto-grants-2013_07
Patent number
US08481738B2

Reaction notes

Loading…