Diisopropylethylamine → HCID 68714832, compound

HRID 506374Notes

Reaction equation

HRID 506374 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH2:18])[CH2:8][C@H:7]1[CH3:19])=[O:5])[CH3:2].[Br:20][C:21]1[CH:22]=[N:23][C:24](Cl)=[N:25][CH:26]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:24]2[N:25]=[CH:26][C:21]([Br:20])=[CH:22][N:23]=2)[CH2:8][C@H:7]1[CH3:19])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 68718350HCID 68718350, compound

Product 1

HCID 68714832HCID 68714832, compoundYield 97.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(2R*,4S*)-4-Amino-6-methoxy-2-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (3.80 g), 5-bromo-2-chloropyrimidin (6.92 g) and N,N-diisopropylethylamine (6.23 ml) are dissolved in 1,4-dioxane (50 ml) and the mixture is heated under reflux for 4 hours. After cooling to room temperature, the reaction solution is partitioned by adding a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=9:1→6:4) to give (2R*,4S*)-4-(5-bromopyrimidin-2-yl)amino-6-methoxy-2-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (5.92 g). MS (m/z): 422/424 [M+H]+

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 4 hours
  3. customthe reaction solution is partitioned
  4. additionby adding a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  5. washThe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=9:1→6:4)

Sources & evidence

ORD record
ord-ad3b5a5476e94ab5ae31503b7c2d27d1
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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