Phosphorus oxychloride → ethyl 5-(1-(4-((tert-butoxycarbonyl)amino)-1H-indazol-1-yl)-1-(4-chlorophenyl)propyl)-1,2,4-oxadiazole-3-carboxylate

HRID 1427273Notes

Reaction equation

[NH2:1][C:2](=[N:8][O:9][C:10](=O)[C:11]([N:21]1[C:29]2[C:24](=[C:25]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:26]=[CH:27][CH:28]=2)[CH:23]=[N:22]1)([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:12][CH3:13])[C:3]([O:5][CH2:6][CH3:7])=[O:4].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:34]([O:33][C:31]([NH:30][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]2[C:24]=1[CH:23]=[N:22][N:21]2[C:11]([C:10]1[O:9][N:8]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[N:1]=1)([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:12][CH3:13])=[O:32])([CH3:37])([CH3:36])[CH3:35]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of the product from Step B above (0.18 g, 0.33 mmol) in pyridine (9.0 mL) was added phosphorus oxychloride (0.25 g, 1.65 mmol). The mixture was heated at 70° C. for 7 hours, and stirred at 35° C. overnight, then concentrated to dryness under reduced pressure. The residue was dissolved in EtOAc and washed with saturated NaHCO3, water and brine. The organic layer was separated and dried over Na2SO4. The crude product was purified on a silica gel column using a gradient of 0-50% ethyl acetate in hexanes to give the title compound as light brown solid. LC/MS m/z=526.1[M+H]+.

Workup

concentrationconcentrated to dryness under reduced pressure
dissolutionThe residue was dissolved in EtOAc
washwashed with saturated NaHCO3, water and brine
customThe organic layer was separated
dry with materialdried over Na2SO4
customThe crude product was purified on a silica gel column

Sources & evidence

ORD record: ord-715bcfc4f05a4332916cbbedd23a61d1
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933113B2

Reaction notes

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