Triethylamine → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

HRID 711482Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 711482
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1.CCN(CC)CC.[NH2:32][C@@H:33]1[CH2:37][CH2:36][CH2:35][C@@H:34]1[NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].C([O-])(O)=O.[Na+]>CN(C=O)C>[C:41]([O:40][C:39]([NH:38][C@H:34]1[CH2:35][CH2:36][CH2:37][C@H:33]1[NH:32][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([S:21]([CH3:24])(=[O:23])=[O:22])[CH:16]=2)[N:3]=1)=[O:45])([CH3:44])([CH3:42])[CH3:43]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 45091940tert-butyl N-[(1S,2R)-2-aminocyclopentyl]carbamateHCID 58317716Methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate

Produkt 1

HCID 67238760Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclopentylamino)-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinateAusbeute 61,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of methyl 6-chloro-4-cyano-2-(3-(methylsulfonyl)phenylamino)nicotinate (165.0 mg, 0.451 mmol), Et3N (0.15 mL, 1.076 mmol), and tert-butyl (1S,2R)-2-aminocyclopentylcarbamate (142.0 mg, 0.709 mmol) in DMF (6 mL) was stirred at 60° C. for 12 h. Saturated aq NaHCO3 (20 mL) was added to the mixture, which was subsequently extracted with EtOAc (2×30 mL). The organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL), were dried over anhydrous Na2SO4, and filtered (DM1020). The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/1) and then triturated with IPE to provide the title compound (147 mg).

Aufarbeitung

  1. extractionwas subsequently extracted with EtOAc (2×30 mL)
  2. washThe organic layers were washed with saturated aq NaHCO3 (20 mL), water (20 mL) and brine (20 mL)
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered (DM1020)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography (SiO2, hexanes/EtOAc=1/1)
  7. customtriturated with IPE

Quellen und Nachweise

ORD-Eintrag
ord-46d411fb2dd94e149f5aa7ddbb23ee7e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181255B2

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