1,2-Dimethoxyethane → 2,4-Dimethyl-6-pyrimidin-5-yl-nicotinic acid ethyl ester

HRID 1711153Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:14])[C:5]1[C:10]([CH3:11])=[CH:9][C:8](Cl)=[N:7][C:6]=1[CH3:13])[CH3:2].[N:15]1[CH:20]=[C:19](B(O)O)[CH:18]=[N:17][CH:16]=1.COCCOC>CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:19]2[CH:20]=[N:15][CH:16]=[N:17][CH:18]=2)=[N:7][C:6]=1[CH3:13])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 6-chloro-2,4-dimethyl-nicotinic acid ethyl ester (0.30 g, 1.40 mmol) and 5-pyrimidine boronic acid (0.522 g, 4.21 mmol) in argon-degassed DME/2 M Na2CO3 (4:1, 12.5 ml) was added Pd(PPh3)4 (162 mg, 0.14 mmol) and the mixture heated to 90° C. overnight. The reaction was cooled, diluted with EtOAc (25 ml) and H2O (15 ml). The aqueous layer was extracted with EtOAc (2×10 ml) and the combined organic extracts were dried (Na2SO4), concentrated and purified by column chromatography on silica gel (Hexanes/EtOAc, 3:2) to afford 2,4-dimethyl-6-pyrimidin-5-yl-nicotinic acid ethyl ester (306 mg, 85%). 1H NMR (CDCl3) δ 1.43 (t, 3H, J=6 Hz), 2.44 (s, 3H), 2.64 (s, 3H), 4.47 (q, 2H, J=6 Hz), 7.44 (s, 1H), 9.26 (s, 1H), 9.32 (s, 2H).

Workup

temperatureThe reaction was cooled
extractionThe aqueous layer was extracted with EtOAc (2×10 ml)
dry with materialthe combined organic extracts were dried (Na2SO4)
concentrationconcentrated
custompurified by column chromatography on silica gel (Hexanes/EtOAc, 3:2)

Sources & evidence

ORD record: ord-9e84e2a96b08470ca3a09187b6a250eb
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790747B2

Reaction notes

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