Chlorotrimethylsilane → 1-[4-chloro-3'-fluoro-5-methyl-6-(4H-1,2,4-triazol-4-yl)biphenyl-2-yl]ethanone

HRID 510851Notes

Reaction equation

[NH:1]([CH:5]=O)[NH:2][CH:3]=O.Cl[Si](C)(C)C.C(N(CC)CC)C.[NH2:19][C:20]1[C:25]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)=[C:24]([C:33](=[O:35])[CH3:34])[CH:23]=[C:22]([Cl:36])[C:21]=1[CH3:37]>N1C=CC=CC=1.O>[Cl:36][C:22]1[C:21]([CH3:37])=[C:20]([N:19]2[CH:3]=[N:2][N:1]=[CH:5]2)[C:25]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)=[C:24]([C:33](=[O:35])[CH3:34])[CH:23]=1

Participants

Conditions

Temperature: 100 °C

Procedure

1,2-Hydrazinedicarboxaldehyde (0.095 g, 1.1 mmol) and then, drop by drop, chlorotrimethylsilane (0.69 mL, 5.4 mmol) and triethylamine (0.35 mL, 2.5 mmol) were added to a suspension of 1-(6-amino-4-chloro-3′-fluoro-5-methylbiphenyl-2-yl)ethanone (0.10 g, 0.36 mmol) in pyridine (2 mL). The mixture was heated at 100° C. overnight. Evaporation at reduced pressure of the solvent yielded a solid that was treated with water and extracted with dichloromethane. The extracts were dried over sodium sulfate and concentrated. The reside was purified on silica gel, eluting with 0 to 50% ethyl acetate in hexane, then 0 to 10% methanol in dichloromethane, to give the desired product (44 mg, 37%). LCMS calculated for C17H14ClFN3O (M+H)+: m/z=330.1. found: 330.0.

Workup

customEvaporation at reduced pressure of the solvent
customyielded a solid
extractionextracted with dichloromethane
dry with materialThe extracts were dried over sodium sulfate
concentrationconcentrated
customThe reside was purified on silica gel
washeluting with 0 to 50% ethyl acetate in hexane

Sources & evidence

ORD record: ord-ecbc05f3f6a64b069a4cd0b66f1302aa
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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