Di-tert-butyl diazene-1,2-dicarboxylate → 1,2-Hydrazinedicarboxylic acid, 1-[4-methoxy-2-(methylthio)-5-pyrimidinyl]-, 1,2-bis(1,1-dimethylethyl) ester

HRID 869074Notes

Reaction equation

HRID 869074 reaction equation
Br[C:2]1[C:3]([O:10][CH3:11])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.[CH3:12][C:13]([O:16][C:17](/[N:19]=[N:20]/[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:18])([CH3:15])[CH3:14]>C1COCC1>[CH3:11][O:10][C:3]1[C:2]([N:19]([C:17]([O:16][C:13]([CH3:15])([CH3:14])[CH3:12])=[O:18])[NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])=[CH:7][N:6]=[C:5]([S:8][CH3:9])[N:4]=1

Participants

4

Reactant 2

HCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 128640905-Bromo-4-methoxy-2-(methylsulfanyl)pyrimidine

Product 1

HCID 896024121,2-Hydrazinedicarboxylic acid, 1-[4-methoxy-2-(methylthio)-5-pyrimidinyl]-, 1,2-bis(1,1-dimethylethyl) esterYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-bromo-4-methoxy-2-(methylthio)pyrimidine (25.3 g, 108 mmol) in THF (250 mL) was added under argon isopropylmagnesium chloride LiCl in THF (108 mL, 140 mmol) at 0° C. The mixture was allowed to warm up to rt and stirred for 1 h. di-tert-butylazodicarboxylate (24.8 g, 108 mmol) was added and the mixture was stirred 1 h at rt, quenched by addition of a saturated aqueous solution of ammonium chloride (250 mL) then extracted with EtOAc. The organic layer was washed with a saturated aqueous solution of ammonium chloride, dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel column chromatography (hexane/EtOAc, 100:0→75:25) to afford 37.2 g of the title compound as a white solid. tR: 1.17 min (LC-MS 4); ESI-MS: 387.3 [M+H]+ (LC-MS 4), Rf=0.79 (hexane/EtOAc, 1:1).

Workup

  1. additionwas added
  2. customquenched by addition of a saturated aqueous solution of ammonium chloride (250 mL)
  3. extractionthen extracted with EtOAc
  4. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc, 100:0→75:25)

Sources & evidence

ORD record
ord-8e77799eb8f24caeb004450d13cc259b
Source dataset
uspto-grants-2015_03
Patent number
US08969341B2

Reaction notes

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