Water → 3-chloromethyl-N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-benzamide

HRID 1803853Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([F:20])[CH:19]=1)[CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[NH2:16].[Cl:21][CH2:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](Cl)=[O:27].O>CC1C=C(C)N=C(C)C=1>[Cl:21][CH2:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([NH:16][C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([O:6][CH2:5][C:4]3[CH:17]=[C:18]([F:20])[CH:19]=[C:2]([F:1])[CH:3]=3)[CH:8]=2)[NH:12][N:11]=1)=[O:27]

Participants

Conditions

Temperature: 4 °C

Procedure

5-(3,5-Difluoro-benzyloxy)-1H-indazol-3-ylamine (550 mg, 2 mmol) was dissolved in sym-collidine, cooled to 4° C. and treated with neat 3-chloromethyl-benzoyl chloride (0.34 mL, 2.4 mmol). After 1 hour the reaction mixture was added drop wise into iced water, with stirring and separation of a yellow oil occurred. Then, EtOAc (50 mL) and 2N HCl (25 mL) were added. The organic phase was separated, washed with aqueous NaHCO3 (50 mL), brine, dried over sodium sulfate and evaporated to dryness. After purification over silica gel (eluent: DCM:MeOH 95:5) 378 mg of title compound were obtained as a whitish solid in 56% yield.

Workup

customseparation of a yellow oil
additionThen, EtOAc (50 mL) and 2N HCl (25 mL) were added
customThe organic phase was separated
washwashed with aqueous NaHCO3 (50 mL), brine
dry with materialdried over sodium sulfate
customevaporated to dryness
customAfter purification over silica gel (eluent: DCM:MeOH 95:5) 378 mg of title compound
customwere obtained as a whitish solid in 56% yield

Sources & evidence

ORD record: ord-f75a9373fc1446e1beb6364fdd07b40d
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354399B2

Reaction notes

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