Phenylhydrazine hydrochloride → 6-Bromo-2-phenyl-2H-indazol-3-ylamine

HRID 1972717Notes

Reaction equation

[Br:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.Cl.[C:12]1([NH:18][NH2:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(C(C)C)CC)(C)C>C(O)CCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:8]([CH:9]=1)=[N:19][N:18]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]=2[NH2:7]

Participants

Conditions

Temperature: 140 °C

Procedure

To a dried flask charged with 4-bromo-2-fluorobenzonitrile (4.0 g, 18.0 mmol) in n-butanol (60 mL) was added a solution of phenylhydrazine hydrochloride (10.4 g, 72.0 mmol, 4.0 eq) and diisopropylethylamine (13.2 mL, 75.6 mmol, 4.2 eq) in n-butanol (35 mL). The reaction mixture was stirred at 140° C. under N2 for 3 days. The mixture was cooled to rt and partitioned between EtOAc and water. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified using an ISCO® instrument (gradient 10 to 65% EtOAc/hexane) and the product containing fractions were concentrated. Crystallization from DCM-hexane afforded 1.33 g (26%) of the title compound as beige solid. 1H NMR (300 MHz, DMSO-d6) δ 7.71 (d, 1H), 7.69 to 7.66 (m, 2H), 7.58 to 7.54 (m, 2H), 7.47 to 7.44 (m, 2H), 6.78 (dd, 1H), 6.50 (s, 2H); ES-MS m/z 288.1/290.1 [M+H]+, RT (min) 2.28.

Workup

temperatureThe mixture was cooled to rt
custompartitioned between EtOAc and water
washThe organic layer was washed with water and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified
additionthe product containing fractions
concentrationwere concentrated
customCrystallization from DCM-hexane

Sources & evidence

ORD record: ord-40fbbf2686ee46dd94d82656190aee30
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431695B2

Reaction notes

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