Hydrochloric Acid → Apalutamide

HRID 1051139Notes

Reaction equation

HRID 1051139 reaction equation
[N:1]([C:4]1[CH:5]=[C:6]([C:12]([F:15])([F:14])[F:13])[C:7]([C:10]#[N:11])=[N:8][CH:9]=1)=[C:2]=[S:3].[C:16]([C:18]1([NH:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=2)[CH2:21][CH2:20][CH2:19]1)#N.C[OH:35].Cl>CN(C=O)C>[C:10]([C:7]1[N:8]=[CH:9][C:4]([N:1]2[C:16](=[O:35])[C:18]3([CH2:21][CH2:20][CH2:19]3)[N:22]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=3)[C:2]2=[S:3])=[CH:5][C:6]=1[C:12]([F:15])([F:13])[F:14])#[N:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 250199805-Isothiocyanato-3-(trifluoromethyl)pyridine-2-carbonitrileHCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide

Product 1

HCID 24872560ApalutamideYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

5-isothiocyanato-3-(trifluoromethyl)pyridine-2-carbonitrile, 9, A is reacted with 4-(1-cyanocyclobutylamino)-2-fluoro-N-methylbenzamide B in DMF solution by heating in a microwave at 80° C. for 20 hours. Methanol and hydrochloric acid are then added and the reaction allowed to proceed for 2 hours to produce 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenzamide, A52 (yield 35 to 87%).

Sources & evidence

ORD record
ord-56c49c0e41844024838ea9b57f603c16
Source dataset
uspto-grants-2016_07
Patent number
US09388159B2

Reaction notes

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