Hydrochloric Acid → Methyl (6-(4-Methylpiperazin-1-yl)-4-(o-tolyl)pyridin-3-yl)carbaMate

HRID 1477266Notes

Reaction equation

[CH3:1][O-:2].[Na+].Br[N:5]1[C:9](=[O:10])CCC1=O.[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:27]=[C:26]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:34])[C:22](C(N)=O)=[CH:21][N:20]=2)[CH2:15][CH2:14]1.Cl>CO.ClCCl>[CH3:1][O:2][C:9](=[O:10])[NH:5][C:22]1[CH:21]=[N:20][C:19]([N:16]2[CH2:15][CH2:14][N:13]([CH3:12])[CH2:18][CH2:17]2)=[CH:27][C:26]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH3:34]

Participants

Conditions

Temperature: -5 °C

Procedure

2.15 mil (11.6 mMol) Sodium methoxide in methanol were added over 30 minutes to a suspension of 0.85 g (4.6 mMol) N-bromosuccinimide in 5.0 ml dichloromethane cooled to −5° C. The reaction mixture was stirred 16 hours at −5° C. Still at this temperature, a solution of 1.0 g (3.1 mMol) 6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide in 5.0 ml methanol was added over 20 minutes and stirred for 5 hours. 7.1 ml (7.1 mMol) Aqueous HCl 1N and 20 ml dichloromethane were added. The phases were separated and the organic phase was washed with deionized water. The aqueous phases were extracted with dichloromethane, brought to pH=8 with aqueous NaOH 1N and further extracted with dichloromethane. The latter organic extracts were combined, dried (Na2SO4) and concentrated to yield 1.08 g (quant.) [6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-carbamic acid methyl ester as a grey foam.

Workup

stirringstirred for 5 hours
customThe phases were separated
washthe organic phase was washed with deionized water
extractionThe aqueous phases were extracted with dichloromethane
extractionfurther extracted with dichloromethane
dry with materialdried (Na2SO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-cc910f548f2749fba2c97a8b6752d40c
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403772B2

Reaction notes

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