Methyl chloroformate → HCID 59447046, compound

HRID 1746793Notes

Reaction equation

HRID 1746793 reaction equation
[CH:1]1([N:7]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([OH:16])=O)[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(NC(C)C)(C)C.ClC(OC)=O.[NH2:33][C:34]1[CH:50]=[CH:49][C:37]([CH2:38][S:39]([CH2:42][CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])(=[O:41])=[O:40])=[CH:36][CH:35]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH:1]1([N:7]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:8]2[N:13]=[CH:12][N:11]=[C:10]([C:14]([NH:33][C:34]3[CH:35]=[CH:36][C:37]([CH2:38][S:39]([CH2:42][CH2:43][C:44]([O:46][CH2:47][CH3:48])=[O:45])(=[O:41])=[O:40])=[CH:49][CH:50]=3)=[O:16])[CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 5

HCID 6586Methyl chloroformateHCID 7912DiisopropylamineHCID 516892Sodium BicarbonateHCID 594468416-[Cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carboxylic acid2×HCID 59446860HCID 59446860, compound2×

Product 1

HCID 59447046HCID 59447046, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A cooled (0° C.) solution of 6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxylic acid (Intermediate 13, 130 mg; 0.47 mmol) in DCM was treated with diisopropylamine (90 mL; 0.52 mmol) and methyl chloroformate (40 mL; 0.52 mmol). After stirring at 0° C. for 15 minutes, ethyl 3-(4-aminobenzylsulfonyl)propanoate (Intermediate 42, 130 mg; 0.48 mmol) was added. After stirring at 0° C. for 30 minutes and RT for 1 hour, saturated sodium bicarbonate solution was added and the mixture stirred for 15 minutes. DCM was added and the layers separated. The organic extract was filtered through a hydrophobic frit and the solvent removed in vacuo. The residue was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give the title compound as an off-white solid.

Workup

  1. stirringAfter stirring at 0° C. for 30 minutes and RT for 1 hour
  2. stirringthe mixture stirred for 15 minutes
  3. customthe layers separated
  4. extractionThe organic extract
  5. filtrationwas filtered through a hydrophobic frit
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by column chromatography (silica)
  8. washeluting with petroleum ether containing
  9. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-c3c90fbe7ba2442cb13d9e0e568c7ee7
Source dataset
uspto-grants-2015_10
Patent number
US09150519B2

Reaction notes

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