2-Chloro-4-methylpyrimidine → 2-Propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]phenyl}carbamate

HRID 239244Notes

Reaction equation

HRID 239244 reaction equation
[CH2:1]([O:4][C:5]([NH:7][C:8]1[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=1)[C:11]([O:13]CC)=O)=[O:6])[CH:2]=[CH2:3].[Cl:19][C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=1>[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1>[Cl:19][C:20]1[N:25]=[C:24]([CH2:26][C:11]([C:10]2[CH:9]=[C:8]([NH:7][C:5](=[O:6])[O:4][CH2:1][CH:2]=[CH2:3])[CH:18]=[CH:17][CH:16]=2)=[O:13])[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 2

HCID 116296072-Chloro-4-methylpyrimidineHCID 57989833Ethyl 3-{[(2-propen-1-yloxy)carbonyl]amino}benzoate

Product 1

HCID 579899812-Propen-1-yl {3-[(2-chloro-4-pyrimidinyl)acetyl]phenyl}carbamateYield 51.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 2733832Lithium HexamethyldisilazideSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 3-{[(2-propen-1-yloxy)carbonyl]amino}benzoate (20.0 g, 80.24 mmol) was dissolved in 1 M LiHMDS in THF (260 mL) and cooled to 0° C. A solution containing 2-chloro-4-methylpyrimidine (10.32 g, 80.24 mmol) in 20 mL dry THF was added to the reaction mixture. The reaction was stirred at 0° C. for 2 h, quenched with MeOH (100 mL), dried directly onto silica, and purified via flash chromatography EtOAc/CH2Cl2 0-100% gradient run over 60 min. The desired fractions were combined and the solvent was removed to give the title compound (13.6 g, 51% yield); ES-LCMS m/z 332 (M+H).

Workup

  1. additionwas added to the reaction mixture
  2. customquenched with MeOH (100 mL)
  3. customdried directly onto silica
  4. custompurified via flash chromatography EtOAc/CH2Cl2 0-100% gradient run over 60 min
  5. customthe solvent was removed

Sources & evidence

ORD record
ord-236d756f44f147668b4d5ed6338fc3b1
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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