Hydrazine hydrate (1:1) → (S)-3-(4-((3-Aminopyridin-4-yl)amino)cyclohexyl)-4-(4-fluorophenyl)-5,5-dimethyloxazolidin-2-one

HRID 525368Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:12]([CH3:14])([CH3:13])[O:11][C:10](=[O:15])[N:9]2[CH:16]2[CH2:21][CH2:20][CH:19]([NH:22][C:23]3[CH:28]=[CH:27][N:26]=[CH:25][C:24]=3[N+:29]([O-])=O)[CH2:18][CH2:17]2)=[CH:4][CH:3]=1.O.NN>[Ni].CCO>[NH2:29][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][C:23]=1[NH:22][CH:19]1[CH2:20][CH2:21][CH:16]([N:9]2[C@@H:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:12]([CH3:13])([CH3:14])[O:11][C:10]2=[O:15])[CH2:17][CH2:18]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a flask charged with (S)-4-(4-fluorophenyl)-5,5-dimethyl-3-(4-((3-nitropyridin-4-yl)amino)cyclohexyl)oxazolidin-2-one (0.285 g, 0.665 mmol) was added EtOH (13.30 mL). Raney 3202 nickel (slurry in water) (0.733 mL, 111 mmol) was then added using a pipette. The flask was sealed, placed under nitrogen, and heated at 40° C. To the resulting yellow solution was added hydrazine hydrate solution (0.311 mL, 9.98 mmol) dropwise. The resulting mixture was stirred for 90 minutes at 40° C. LC-MS indicated complete conversion to the desired product. The mixture was cooled to room temperature, filtered through Celite® brand filter aid, and washed with MeOH. The filtrate was dried under reduced pressure and was then purified using a 5 g SCX-2 column washing with MeOH and then with 2 M NH3 in MeOH. The basic wash was dried under reduced pressure providing a brown oil which solidified after overnight under high vacuum to yield (S)-3-(4-((3-aminopyridin-4-yl)amino)cyclohexyl)-4-(4-fluorophenyl)-5,5-dimethyloxazolidin-2-one (0.213 g, 0.535 mmol, 80% yield) as a yellow solid. m/z (ESI) 399.0 (M+H)+.

Workup

customThe flask was sealed

Sources & evidence

ORD record: ord-65ec5c5090e14ef4bd893e011f347494
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340549B2

Reaction notes

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