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

HRID 1946791

Reaktionsgleichung

Reaktionsgleichung von HRID 1946791
ClC1N=CN=C(C(NC2C=CC(S(NCC(OC)=O)(=O)=O)=CC=2C)=O)C=1.C(NC(C)C)(C)C.C1(CNCCC)CC1.[CH:42]1([CH2:45][N:46]([CH2:72][CH2:73][CH3:74])[C:47]2[N:52]=[CH:51][N:50]=[C:49]([C:53]([NH:55][C:56]3[CH:61]=[CH:60][C:59]([S:62]([NH:65][CH2:66][C:67]([O:69]C)=[O:68])(=[O:64])=[O:63])=[CH:58][C:57]=3[CH3:71])=[O:54])[CH:48]=2)[CH2:44][CH2:43]1.C1(CN(CCC)C2N=CN=C(C(NC3C=CC(S(NCC(OCC)=O)(=O)=O)=CC=3C)=O)C=2)CC1>C(O)C>[CH:42]1([CH2:45][N:46]([CH2:72][CH2:73][CH3:74])[C:47]2[N:52]=[CH:51][N:50]=[C:49]([C:53]([NH:55][C:56]3[CH:61]=[CH:60][C:59]([S:62]([NH:65][CH2:66][C:67]([OH:69])=[O:68])(=[O:63])=[O:64])=[CH:58][C:57]=3[CH3:71])=[O:54])[CH:48]=2)[CH2:44][CH2:43]1

Komponenten

7

Edukt 5

HCID 7912DiisopropylamineHCID 117787Cyclopropanemethanamine, N-propyl-HCID 59446920Methyl 2-(4-(6-chloropyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate2×HCID 67529258Methyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetateHCID 68487588Ethyl 2-(4-(6-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate

Produkt 1

HCID 46881536N-({4-[({6-[(cyclopropylmethyl)(propyl)amino]pyrimidin-4-yl}carbonyl)amino]-3-methylphenyl}sulfonyl)glycine

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)propan-1-amine (45.3 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-((cyclopropylmethyl)(propyl)amino)pyrimidine-4-carboxamido)-3-methylphenylsulfonamido)acetate and ethyl 2-(4-(6-((cyclopropylmethyl)(propyl)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.

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-404a731582584c97918505bd4a6af0c4
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399448B2

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