Sodium Carbonate → tert-butyl N-[6-[(E)-2-cyclopropylvinyl]pyrimidin-4-yl]carbamate

HRID 1050333Notes

Reaction equation

HRID 1050333 reaction equation
Cl[C:2]1C(=O)N[C:5]([C:9](OCC)=O)=[CH:4][CH:3]=1.C(OC([N:21]([C:29]1[CH:34]=[C:33](Cl)[N:32]=[CH:31][N:30]=1)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=O)(C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[CH:4]1(/[CH:3]=[CH:2]/[C:33]2[N:32]=[CH:31][N:30]=[C:29]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:34]=2)[CH2:5][CH2:9]1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 45790082N,N-DiBoc-4-amino-6-chloropyrimidineHCID 46311507Ethyl 5-chloro-6-oxo-1,6-dihydropyridine-2-carboxylate

Product 1

HCID 118598978tert-butyl N-[6-[(E)-2-cyclopropylvinyl]pyrimidin-4-yl]carbamate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of [(E)-2-cyclopropylvinyl]boronic acid (1, 1.0 g, 8.93 mmol), tert-butyl N-tert-butoxycarbonyl-N-(6-chloropyrimidin-4-yl)carbamate (2, 3.24 g, 9.83 mmol), sodium carbonate (2.84 g, 26.8 mmol), 1,4-dioxane (10 mL) and water (3 mL) in a microwave vial was degassed with argon for 10 minutes. To this mixture 1,1-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.73 g, 0.89 mmol) was added and purged with argon for 5 minutes. After sealing, the vial was irradiated in a microwave reactor at 130° C. for 45 minutes. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×30 mL). The organics were washed with water (2×10 mL) and saturated brine solution (1×10 mL). The organics were then separated, dried with sodium sulfate, and filtered before concentration to dryness. The crude residue was purified by column chromatography (silica, ethyl acetate/hexanes=25%) to obtain tert-butyl N-[6-[(E)-2-cyclopropylvinyl]pyrimidin-4-yl]carbamate (3) as a light brown solid. Yield: 370 mg, 16%; MS (ESI) m/z 262.22 [M+1-Boc]+; 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 8.60 (s, 1H), 7.63 (s, 1H), 6.50 (m, 2H), 1.48 (s, 9H), 0.91 (m, 2H), 0.64 (m, 2H)

Workup

  1. customwas degassed with argon for 10 minutes
  2. additionTo this mixture 1,1-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.73 g, 0.89 mmol) was added
  3. custompurged with argon for 5 minutes
  4. customthe vial was irradiated in a microwave reactor at 130° C. for 45 minutes
  5. additionThe reaction mixture was diluted with water (20 mL)
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. washThe organics were washed with water (2×10 mL) and saturated brine solution (1×10 mL)
  8. customThe organics were then separated
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered before concentration to dryness
  11. customThe crude residue was purified by column chromatography (silica, ethyl acetate/hexanes=25%)

Sources & evidence

ORD record
ord-6d631f51fefd43b6a5311fc5bd61ff1d
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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