2-Amino-3-bromopyridine → Benzyl 4-[2-[(3-bromopyridin-2-yl)amino]-2-oxoethyl}-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1671602Notes

Reaction equation

CO[C:3](=[O:21])[CH2:4][C:5]1[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:9][CH:10]=1.[NH2:22][C:23]1[C:28]([Br:29])=[CH:27][CH:26]=[CH:25][N:24]=1>ClCCCl>[Br:29][C:28]1[C:23]([NH:22][C:3](=[O:21])[CH2:4][C:5]2[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:12])[CH2:9][CH:10]=2)=[N:24][CH:25]=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 55 °C

Procedure

Timethylaluminum (2.0 M, 2.05 mL, 4.10 mol) was added slowly to a 0° C. solution of benzyl 4-(2-methoxy-2-oxoethyl)-3,6-dihydropyridine-1(2H)-carboxylate (0.79 g, 2.73 mol) and 2-amino-3-bromopyridine (0.520 g, 3.00 mmol) in 1,2-dichloroethane (15 mL). After 30 min, the reaction was heated to 55° C. for 48 h. The reaction was quenched by the careful addition of saturated aqueous sodium bicarbonate and the mixture extracted with dichlormethane (4×). The combined organic layers were washed with 1N sodium potassium tartrate, brine, dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of 50 to 100% ethyl acetate:hexanes to give the title compound (2.44 g). MS: m/z=430.0 (M+1).

Workup

customThe reaction was quenched by the careful addition of saturated aqueous sodium bicarbonate
extractionthe mixture extracted with dichlormethane (4×)
washThe combined organic layers were washed with 1N sodium potassium tartrate, brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by silica gel chromatography
washeluting with a gradient of 50 to 100% ethyl acetate

Sources & evidence

ORD record: ord-c78a96b6354e42529c789c2c59351c10
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994325B2

Reaction notes

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