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

HRID 1664770Notes

Reaction equation

HRID 1664770 reaction equation
C[Al](C)C.CO[C:7](=[O:25])[CH2:8][C:9]1[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:13][CH:14]=1.[NH2:26][C:27]1[C:32]([Br:33])=[CH:31][CH:30]=[CH:29][N:28]=1>ClCCCl>[Br:33][C:32]1[C:27]([NH:26][C:7](=[O:25])[CH2:8][C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:16])[CH2:13][CH:14]=2)=[N:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 8177002-Amino-3-bromopyridineHCID 16682925TrimethylaluminumHCID 59555173Benzyl 4-(2-methoxy-2-oxoethyl)-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 59555280Benzyl 4-[2-[(3-bromopyridin-2-yl)amino]-2-oxoethyl}-3,6-dihydropyridine-1(2H)-carboxylateYield 189%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
55 °C

Procedure

Trimethylaluminum (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

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

Sources & evidence

ORD record
ord-171773d38afd4bd4adcce76cbeab4beb
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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