Diisopropylethylamine → (R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-methoxypropylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

HRID 516089Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516089
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1.[NH2:20][CH2:21][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:23][O:24][CH3:25].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:29]([O:28][C:27]([NH:26][C@@H:22]([CH2:23][O:24][CH3:25])[CH2:21][NH:20][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1)=[O:33])([CH3:32])([CH3:31])[CH3:30]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 58317582methyl 6-chloro-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinateHCID 59199768tert-butyl N-((2R)-1-amino-3-methoxypropan-2-yl)carbamate

Produkt 1

HCID 67238066(R)-Methyl 6-(2-(tert-butoxycarbonylamino)-3-methoxypropylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

To a screw-top vial was added methyl 6-chloro-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (115 mg, 0.416 mmol), (R)-tert-butyl 1-amino-3-methoxypropan-2-ylcarbamate (93 mg, 0.457 mmol), and DIPEA (87 μL, 0.499 mmol) in DMF (308 μL). The resulting yellow solution was stirred for 12 h at 45° C. and then at 50° C. for 6 h. The reaction mixture was diluted with EtOAc (20 mL) and was washed with water (10 mL) and brine (20 mL). The organic layer was collected and dried over Na2SO4 and was concentrated to a yellow oil. The concentrate was purified via standard phase column chromatography eluting with EtOAc and hexanes (50-100% EtOAc gradient) to give the title compound as a light yellow residue (36.5 mg, 20%). [M+H] calc'd for C21H28N6O5, 445; found, 445.

Aufarbeitung

  1. waitat 50° C. for 6 h
  2. washwas washed with water (10 mL) and brine (20 mL)
  3. customThe organic layer was collected
  4. dry with materialdried over Na2SO4
  5. concentrationwas concentrated to a yellow oil
  6. customThe concentrate was purified via standard phase column chromatography
  7. washeluting with EtOAc and hexanes (50-100% EtOAc gradient)

Quellen und Nachweise

ORD-Eintrag
ord-077eb8afb6494fa1bf9eda26517cd819
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108970B2

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