Diisopropylamine → Ethyl 4-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)butanoate

HRID 1746740Notes

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]([NH:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])(=[O:19])=[O:18])=[CH:13][C:12]=2[CH3:29])=[O:9])[CH:3]=1.C(NC(C)C)(C)C.[CH:37]1([CH2:40][NH:41][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)[CH2:39][CH2:38]1>C(O)C>[CH:42]1([N:41]([CH2:40][CH:37]2[CH2:38][CH2:39]2)[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]([NH:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])(=[O:19])=[O:18])=[CH:13][C:12]=3[CH3:29])=[O:9])[CH:3]=2)[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]1

Participants

Conditions

Temperature: 160 °C

Procedure

A solution of ethyl 4-(4-(6-chloropyrimidine-4-carboxamido)-3-methylphenylsulfonamido)butanoate (Intermediate 35, 123 mg; 0.31 mmol) and diisopropylamine (105.5 mL; 0.61 mmol) in ethanol (4 ml) was treated with N-(cyclopropylmethyl)cyclohexanamine (56.6 mg, 0.4 mmol). The mixture was heated to 160° C. in a microwave for 1 hour and the solvent removed in vacuo. The residue purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give ethyl 4-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)butanoate which was used directly without any further purification. The residue was dissolved in methanol (10 ml) and THF (10 ml) and treated with 5 N NaOH solution (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 concentrated 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 a white solid (120 mg, 73%).

Workup

customthe solvent removed in vacuo
customThe residue purified by column chromatography (silica)
washeluting with petroleum ether containing
temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record: ord-c2c274fbb8ea4d7b873e6c987df7da70
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150519B2

Reaction notes

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