Acetic Acid → methyl (2S)-3-[4-(3-{[4-(1-fluoroethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanoate

HRID 595151Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH:8]([F:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.C(O)(=O)C.[NH2:15][C:16]1[CH:17]=[C:18]([C:23]2[CH:24]=[N:25][N:26]([CH2:28][C@H:29]([OH:34])[C:30]([O:32][CH3:33])=[O:31])[CH:27]=2)[CH:19]=[C:20]([CH3:22])[CH:21]=1>O1CCOCC1.O>[F:10][CH:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:15][C:16]2[CH:17]=[C:18]([C:23]3[CH:24]=[N:25][N:26]([CH2:28][C@H:29]([OH:34])[C:30]([O:32][CH3:33])=[O:31])[CH:27]=3)[CH:19]=[C:20]([CH3:22])[CH:21]=2)[N:7]=1)[CH3:9]

Participants

Conditions

Temperature: 120 °C

Procedure

2-Chloro-4-(1-fluoroethyl)pyrimidine (58 mg, 0.36 mmol) and acetic acid (0.022 mL, 0.38 mmol) were added to an oven-dried flask containing methyl (2S)-3-[4-(3-amino-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanoate (100 mg, 0.36 mmol) in dioxane (1.2 mL). The mixture was stirred for 3 hours at 120° C. then cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (2 to 100% EtOAc/hexanes) to afford methyl (2S)-3-[4-(3-{[4-(1-fluoroethyl)pyrimidin-2-yl]amino}-5-methylphenyl)-1H-pyrazol-1-yl]-2-hydroxypropanoate. MS ESI calcd. for C20H23FN5O3 [M+H]+ 400. found 400.

Workup

temperaturethen cooled to room temperature
extractionextracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (2 to 100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-a5906c11644c452f8e73e3b26b4ab783
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242984B2

Reaction notes

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