Diisopropylethylamine → 1,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate

HRID 473318Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 473318
Cl[C:2]1[N:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[NH2:13][CH2:14][C@:15]1([F:28])[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[Cl:12][C:10]1[CH:9]=[C:8]2[C:3]([CH:4]=[CH:5][CH:6]=[N:7]2)=[C:2]([NH:13][CH2:14][C@:15]2([F:28])[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16]2)[N:11]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 122042335,7-Dichloro-1,6-naphthyridineHCID 68210002tert-Butyl (R)-3-(aminomethyl)-3-fluoropiperidine-1-carboxylate

Produkt 1

HCID 866768011,1-Dimethylethyl (3R)-3-{[(7-chloro-1,6-naphthyridin-5-yl)amino]methyl}-3-fluoro-1-piperidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To 5,7-dichloro-1,6-naphthyridine (5.01 g, 25.2 mmol) and 1,1-dimethylethyl (3R)-3-(aminomethyl)-3-fluoro-1-piperidinecarboxylate (5.32 g, 22.90 mmol) in NMP (20 ml) was added DIPEA (8.00 ml, 45.8 mmol) and the mixture was stirred at 100° C. for 72 h under nitrogen. The reaction was cooled and partitioned between ethyl acetate and water (200 ml each). The aqueous was washed with ethyl acetate. The combined organics were washed with water and the solvent was removed. The residue was dissolved in DCM and loaded onto a 100 g silica SNAP column and purified on the SP4 eluting with 0-50% ethyl acetate in cyclohexane over 17 CVs. Appropriate fractions were combined and the solvent was removed to give the title compound as a pale orange solid which was dried under high vacuum for 2 h (7.61 g).

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water (200 ml each)
  3. washThe aqueous was washed with ethyl acetate
  4. washThe combined organics were washed with water
  5. customthe solvent was removed
  6. dissolutionThe residue was dissolved in DCM
  7. custompurified on the SP4
  8. washeluting with 0-50% ethyl acetate in cyclohexane over 17 CVs
  9. customthe solvent was removed

Quellen und Nachweise

ORD-Eintrag
ord-26504d44e3254af3a4a85fe74888d429
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633319B2

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