Methyl chloroformate → Ethyl 4-({4-[({6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidin-4-yl}carbonyl)amino]phenyl}sulfonyl)butanoate

HRID 1746794Notes

Reaction equation

HRID 1746794 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:39]=[CH:38][C:37]([S:40]([CH2:43][CH2:44][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])(=[O:42])=[O:41])=[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:39]=[CH:38][C:37]([S:40]([CH2:43][CH2:44][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])(=[O:42])=[O:41])=[CH:36][CH:35]=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 59446984Ethyl 4-(4-aminophenylsulfonyl)butanoate2×

Product 1

HCID 59447011Ethyl 4-({4-[({6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidin-4-yl}carbonyl)amino]phenyl}sulfonyl)butanoate

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 4-(4-aminophenylsulfonyl)butanoate (Intermediate 48, 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 a 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-fd43833c6f374b53b00db34e190f1e32
Source dataset
uspto-grants-2015_10
Patent number
US09150519B2

Reaction notes

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