Diisopropylamine → N-({4-[({6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidin-4-yl}carbonyl)amino]-3-methylphenyl}sulfonyl)glycine

HRID 1946757Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1946757
ClC1N=CN=C(C(NC2C=CC(S(NCC(OC)=O)(=O)=O)=CC=2C)=O)C=1.C(NC(C)C)(C)C.C1(CNC2CCCCC2)CC1.[CH:45]1([N:51]([CH2:77][CH:78]2[CH2:80][CH2:79]2)[C:52]2[N:57]=[CH:56][N:55]=[C:54]([C:58]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([S:67]([NH:70][CH2:71][C:72]([O:74]C)=[O:73])(=[O:69])=[O:68])=[CH:63][C:62]=3[CH3:76])=[O:59])[CH:53]=2)[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1.C1(N(CC2CC2)C2N=CN=C(C(NC3C=CC(S(NCC(OCC)=O)(=O)=O)=CC=3C)=O)C=2)CCCCC1>C(O)C>[CH:45]1([N:51]([CH2:77][CH:78]2[CH2:79][CH2:80]2)[C:52]2[N:57]=[CH:56][N:55]=[C:54]([C:58]([NH:60][C:61]3[CH:66]=[CH:65][C:64]([S:67]([NH:70][CH2:71][C:72]([OH:74])=[O:73])(=[O:69])=[O:68])=[CH:63][C:62]=3[CH3:76])=[O:59])[CH:53]=2)[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1

Komponenten

7

Edukt 5

HCID 7912DiisopropylamineHCID 1531432N-(cyclopropylmethyl)cyclohexanamineHCID 59446920Methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate2×HCID 67529295Ethyl 2-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetateHCID 67530211Methyl 2-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate

Produkt 1

HCID 25182909N-({4-[({6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidin-4-yl}carbonyl)amino]-3-methylphenyl}sulfonyl)glycineAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A solution of methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate (Intermediate 33, 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 was purified by column chromatography (silica) eluting with petroleum ether containing increasing amounts of EtOAc to give a mixture of methyl 2-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate and ethyl 2-(4-(6-(cyclohexyl(cyclopropylmethyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate which was used directly without any further purification. The residue was redissolved in methanol (10 ml) and tetrahydrofuran (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 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 a white solid (136 mg, 87%).

Aufarbeitung

  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
  5. customto give
  6. customwas used directly without any further purification
  7. dissolutionThe residue was redissolved in methanol (10 ml)
  8. additiontetrahydrofuran (10 ml) and treated with 5 N NaOH solution (1 ml)
  9. customwas removed in vacuo
  10. dissolutionThe residue was redissolved in water (10 ml)
  11. extractionThe aqueous phase was extracted with EtOAc
  12. customthe solvent removed in vacuo
  13. customThe residue was triturated with petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-65116ec35adc4f7c88fd0a4cdbf573a8
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399448B2

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