1,2-Dimethoxyethane → methyl 4-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-methylbenzoate

HRID 596082Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=2)=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O>[NH2:1][C:2]1[C:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=2)=[CH:6][C:5]([C:24]2[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=2)=[CH:4][N:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To methyl 4-(2-amino-5-bromopyridin-3-yl)-2-methylbenzoate (500 mg, 1.557 mmol) in 20 mL MW vial was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (421 mg, 2.024 mmol), PdCl2(dppf)DCM (114 mg, 0.156 mmol), DME (11.7 mL) and 2 M Na2CO3 solution (3.892 mL). The reaction mixture was heated at microwave synthesizer (12 min, 120° C.). The reaction mixture was diluted with EtOAc and washed with water three times, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography eluting with 0-100% of EtOAc (containing 10% of MeOH)/heptane to provide crude product which was triturated with ether to provide 400 mg of pure product in 80% yield. LCMS (m/z): 323.4 (MH+), 0.60 min.

Workup

washwashed with water three times
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography
washeluting with 0-100% of EtOAc (containing 10% of MeOH)/heptane
customto provide crude product which
customwas triturated with ether

Sources & evidence

ORD record: ord-00d6701e1368472c9429b9f49f8aa8b1
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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