1,3-Dichloroacetone → 4-[(4-{[(6-Amino-3,5-dicyano-4-{4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]phenyl}pyridin-2-yl)thio]methyl}-1,3-thiazol-2-yl)amino]benzoic acid

HRID 2362809

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([NH2:13])=[S:12])=[CH:6][CH:5]=1)([OH:3])=[O:2].Cl[CH2:15][C:16]([CH2:18]Cl)=O.[NH2:20][C:21]1[C:26]([C:27]#[N:28])=[C:25]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH:37]3[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38]3)=[CH:31][CH:30]=2)[C:24]([C:44]#[N:45])=[C:23]([SH:46])[N:22]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:20][C:21]1[N:22]=[C:23]([S:46][CH2:18][C:16]2[N:13]=[C:11]([NH:10][C:7]3[CH:6]=[CH:5][C:4]([C:1]([OH:3])=[O:2])=[CH:9][CH:8]=3)[S:12][CH:15]=2)[C:24]([C:44]#[N:45])=[C:25]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH:37]3[CH2:41][O:40][C:39]([CH3:42])([CH3:43])[O:38]3)=[CH:31][CH:30]=2)[C:26]=1[C:27]#[N:28]

Participants

Conditions

Temperature: 100 °C

Procedure

177 mg (0.90 mmol) of 4-carboxyphenylthiourea and 111 mg (0.87 mmol) of 1,3-dichloroacetone are dissolved in 3 ml of DMF, and the reaction solution is stirred at 100° C. for 60 min. After cooling, 230 mg (0.60 mmol) of the compound from Example 3A and 151 mg (1.80 mmol) of sodium bicarbonate are added, and the mixture is stirred at RT for a further 16 h. The reaction mixture is purified directly by preparative HPLC chromatography (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).

Workup

temperatureAfter cooling
stirringthe mixture is stirred at RT for a further 16 h
customThe reaction mixture is purified directly by preparative HPLC chromatography (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5)

Sources & evidence

ORD record: ord-e44f1fb762ea4f54bf275d9b7de39cfd
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691850B2

Linked notes

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