Diisopropylamine → methyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate

HRID 1746771Notes

Reaction equation

HRID 1746771 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([S:17]([N:20]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH3:21])(=[O:19])=[O:18])=[CH:13][C:12]=2[CH3:27])=[O:9])[CH:3]=1.C(NC(C)C)(C)C.[CH:35]1([CH2:38][NH:39][CH2:40][CH2:41][CH3:42])[CH2:37][CH2:36]1>CO>[CH:35]1([CH2:38][N:39]([CH2:40][CH2:41][CH3:42])[C:2]2[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([S:17]([N:20]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[CH3:21])(=[O:19])=[O:18])=[CH:13][C:12]=3[CH3:27])=[O:9])[CH:3]=2)[CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 117787Cyclopropanemethanamine, N-propyl-HCID 59446951methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate2×

Product 1

HCID 68485880methyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
160 °C

Procedure

A solution of methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate (Intermediate 36, 123 mg; 0.30 mmol) and diisopropylamine (105.5 mL; 0.61 mmol) in methanol (4 ml) was treated with N-(cyclopropylmethyl)propan-1-amine (45.3 mg; 0.4 mmol). The mixture was heated to 160° C. in a microwave for 1 hour and then the solvent removed in vacuo. The residue was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give methyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-N,3-dimethylphenylsulfonamido)acetate which was used directly without any further purification. The residue was redissolved in methanol (10 ml) and THF (10 ml) and treated with 5 N NaOH (1 ml). After stirring at RT for 5 hours the solvent was removed in vacuo. The residue was redissolved in water (10 ml) and acidified with conc. HCl. The aqueous phase was extracted with EtOAc and the organic extracts passed through a hydrophobic frit and the solvent removed in vacuo. The residue was triturated with petroleum ether to yield the title compound as an off-white solid.

Workup

  1. customthe solvent removed in vacuo
  2. customThe residue was purified by column chromatography (silica)
  3. washeluting with petroleum ether containing
  4. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-a30567f68caf441b8efb5ef8c0e66c46
Source dataset
uspto-grants-2015_10
Patent number
US09150519B2

Reaction notes

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