Potassium Carbonate → 6-(2,4-Difluorophenoxy)-8-((r)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one

HRID 2353309Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 4-((R)-2-hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde (17.7 g, 78 mmol) and (2,4-difluorophenoxy)acetic acid methyl ester (31.6 g, 156 mmol) in anhydrous dimethyl formamide (300 mL) was added potassium carbonate (30 g, 218 mmol). The reaction mixture was heated to 60° C. and after 18 hours, reaction mixture was cooled and DMF was distilled off. Residue suspended in water (300 mL) and extracted with dichloromethane, washed with brine and dried over magnesium sulfate. Filtered and concentrated under vacuum to give 29.5 g crude material which was chromatographed on silica gel column eluding with 1% methanol in dichloromethane to give 17.5 g 6-(2,4-difluorophenoxy)-8-((R)-2-hydroxypropyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (mass spec M+1=274).

Workup

customreaction mixture
temperaturewas cooled
distillationDMF was distilled off
extractionextracted with dichloromethane
washwashed with brine
dry with materialdried over magnesium sulfate
filtrationFiltered
concentrationconcentrated under vacuum
customto give 29.5 g crude material which
customwas chromatographed on silica gel column eluding with 1% methanol in dichloromethane

Sources & evidence

ORD record: ord-a9ba80e148784a70a90f994504bf4bc2
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750016B2

Reaction notes

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