2-Amino-6-(benzylthio)-4-(4-hydroxyphenyl)pyridine-3,5-dicarbonitrile → 2-Amino-6-(benzylthio)-4-{4-[2-(dimethylamino)ethoxy]phenyl}pyridine-3,5-dicarbonitrile

HRID 2362814Notes

Reaction equation

HRID 2362814 reaction equation
CC(C)([O-])C.[K+].[NH2:7][C:8]1[C:13]([C:14]#[N:15])=[C:12]([C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)[C:11]([C:23]#[N:24])=[C:10]([S:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:9]=1.Cl.[CH3:34][N:35]([CH3:39])[CH2:36][CH2:37]Cl>C(O)C>[NH2:7][C:8]1[C:13]([C:14]#[N:15])=[C:12]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH2:37][CH2:36][N:35]([CH3:39])[CH3:34])=[CH:20][CH:21]=2)[C:11]([C:23]#[N:24])=[C:10]([S:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:9]=1

Participants

5

Reactant 3

HCID 3981622-Amino-6-(benzylthio)-4-(4-hydroxyphenyl)pyridine-3,5-dicarbonitrileHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 687062052-Amino-6-(benzylthio)-4-{4-[2-(dimethylamino)ethoxy]phenyl}pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6.31 g (56.2 mmol) of potassium tert-butoxide are added to a solution of 8.39 g (23.4 mmol) of 2-amino-6-(benzylthio)-4-(4-hydroxyphenyl)pyridine-3,5-dicarbonitrile [preparation according to WO 01/25210, Example A 383, from 2-amino-4-(4-hydroxyphenyl)-6-mercaptopyridine-3,5-dicarbonitrile and benzyl bromide] in 105.5 ml of ethanol. The mixture is stirred at RT for 1 h, and 4.05 g (28.1 mmol) of 2-dimethylaminoethyl chloride hydrochloride are then added. The mixture is then stirred at +78° C. for 3 h. After cooling, the reaction mixture is filtered and the filtrate is concentrated using a rotary evaporator. The residue is purified directly by preparative HPLC (column: Merck 210 g RP silica gel Gromsil 1200DS-4 HR 10 μm, 50 mm×200 mm; mobile phase A=water+0.1% formic acid, mobile phase B=acetonitrile; gradient: 0 min 10% B→5 min 10% B→6 min 90% B→22 min 90% B→22 min 10% B→28 min 10% B; flow rate: 110 ml/min; wavelength: 220 nm).

Workup

  1. stirringThe mixture is then stirred at +78° C. for 3 h
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture is filtered
  4. concentrationthe filtrate is concentrated
  5. customa rotary evaporator
  6. customThe residue is purified directly by preparative HPLC (column: Merck 210 g RP silica gel Gromsil 1200DS-4 HR 10 μm, 50 mm×200 mm; mobile phase A=water+0.1% formic acid, mobile phase B=acetonitrile; gradient: 0 min 10% B→5 min 10% B→6 min 90% B→22 min 90% B→22 min 10% B→28 min 10% B; flow rate: 110 ml/min; wavelength: 220 nm)

Sources & evidence

ORD record
ord-a535ca7cd9d84f569372f99cd4e15b1c
Source dataset
uspto-grants-2014_04
Patent number
US08691850B2

Reaction notes

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