3-(Dimethylamino)acrylaldehyde → Tert-butyl 3-(1,1-dimethylethylsulfinamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

HRID 509558Notes

Reaction equation

HRID 509558 reaction equation
[C:1]([C:4]1([NH:15][S:16]([C:18]([CH3:21])([CH3:20])[CH3:19])=[O:17])[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1)(=[NH:3])[NH2:2].C[O-].[Na+].CN(C)/[CH:27]=[CH:28]/[CH:29]=O>CO>[CH3:19][C:18]([CH3:21])([S:16]([NH:15][C:4]1([C:1]2[N:2]=[CH:29][CH:28]=[CH:27][N:3]=2)[CH2:5][N:6]([C:8]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[O:9])[CH2:7]1)=[O:17])[CH3:20]

Participants

5

Reactant 3

HCID 6383203-(Dimethylamino)acrylaldehydeHCID 10942334Sodium MethoxideHCID 89835483Tert-butyl 3-carbamimidoyl-3-(1,1-dimethylethylsulfinamido)azetidine-1-carboxylate

Product 1

HCID 89825281Tert-butyl 3-(1,1-dimethylethylsulfinamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylateYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To the above reaction mixture of tert-butyl 3-carbamimidoyl-3-(1,1-dimethylethylsulfinamido)azetidine-1-carboxylate (assumed 4.98 mmol) in methanol (5 mL) was added sodium methoxide (0.509 g, 9.42 mmol) and (E)-3-(dimethylamino)acrylaldehyde (0.560 g, 5.65 mmol), and the resulting solution was heated at 70° C. overnight. The reaction mixture was then concentrated and the residue dissolved in ethyl acetate. The mixture was washed with water followed by saturated brine solution, and then dried over Na2SO4 and concentrated. The crude product was then purified by column chromatography (50% EtOAc in Hexane) to afford tert-butyl 3-(1,1-dimethylethylsulfinamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate Yield: 200 mg (overall 12%). 1H NMR (400 MHz, CDCl3): δ 8.78 (d, J=4.8 Hz, 2H), 7.24 (m, 1H), 4.63-4.48 (m, 2H), 4.23 (d, J=9.2 Hz, 2H), 1.47 (s, 9H), 1.29 (s, 9H). LCMS: (ES+) m/z observed=255.2 (M+H)+ of 2-methyl-N-(3-(pyrimidin-2-yl)azetidin-3-yl)propane-2-sulfinamide.

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutionthe residue dissolved in ethyl acetate
  3. washThe mixture was washed with water
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was then purified by column chromatography (50% EtOAc in Hexane)

Sources & evidence

ORD record
ord-ee5e53443b2e4feb84c6ce9a579fc8c4
Source dataset
uspto-grants-2015_08
Patent number
US09096580B2

Reaction notes

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