Diisopropylethylamine → 7-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid methyl ester

HRID 450119Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:24])[CH:4]([CH2:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][N:19]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[CH:10][C:9]=1[F:16])=O.C(N(C(C)C)CC)(C)C.O(Cl)Cl.[P+5]>O1CCOCC1>[CH3:1][O:2][C:3]([C:4]1[CH:17]=[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]2[C:5]=1[NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH3:15])=[CH:10][C:9]=1[F:16])=[O:24]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of N-(2-fluoro-4-methylsulfanyl-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid methyl ester (2 g, 5.72 mmol) and diisopropylethyl amine (2.9 mL, 17.2 mmol) in dioxane (30 mL) was added phosphorous (V) oxychloride (2.7 mL, 28.6 mmol) and the reaction mixture heated at reflux for 1 hour. The reaction mixture was cooled to 0° C. and quenched with water (10 mL). The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (3×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 10-20% ethylacetate in cyclohexane) to yield the title compound as a light brown solid (0.80 g, 42%). LCMS (Method B): RT=3.70 min, M+H+=332.

Workup

temperaturethe reaction mixture heated
temperatureat reflux for 1 hour
customquenched with water (10 mL)
additionThe reaction mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL)
extractionextracted with ethyl acetate (3×10 mL)
washThe combined organic fractions were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-045306fa0ec2457085b46f4e35388be4
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486963B2

Reaction notes

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