Triethylamine → Benzyl 4-((5-chloro-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate

HRID 384691Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 384691
Cl[C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=1.[NH2:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:20][CH2:19]1.C(N(CC)CC)C>CN1C(=O)CCC1.CO>[NH3:5].[Cl:8][C:7]1[C:2]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[CH2:20][CH2:19]2)=[CH:3][C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[N:5][CH:6]=1

Komponenten

7

Edukt 3

HCID 8471TriethylamineHCID 10538422N-(4,5-Dichloropyridin-2-yl)pivalamideHCID 219554994-Aminomethyl-1-N-Cbz-piperidine

Produkt 2

HCID 222AmmoniaHCID 59613350Benzyl 4-((5-chloro-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylateAusbeute 150 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
210 °C

Versuchsvorschrift

A capped microwave reaction vial containing a solution of N-(4,5-dichloropyridin-2-yl)pivalamide (0.38 g, 1.54 mmol) (Synthesis 153-B), benzyl 4-(aminomethyl)piperidine-1-carboxylate (0.76 g, 2 eq) and triethylamine (0.43 mL, 2 eq) in NMP (3 mL) was heated at 210° C. for 1.75 hr under microwave irradiation, and then allowed to cooled. The reaction mixture was diluted with MeOH and adsorbed onto Isolute SCX-II acidic resin (10 g). The resin was washed with methanol, then 2M ammonia in methanol. The basic fractions were concentrated and the crude product was further purified by column chromatography, using a Biotage 40+silica column eluted with a gradient of EtOAc in hexane. The product contained residual NMP which was removed by a second ion exchange purification on Isolute SCX-II acidic resin, eluting with methanol, then 2M ammonia in methanol, to give benzyl 4-((5-chloro-2-pivalamidopyridin-4-ylamino)methyl)piperidine-1-carboxylate as a light yellow gum (0.53 g, 68%).

Aufarbeitung

  1. customA capped microwave reaction
  2. temperatureto cooled
  3. washThe resin was washed with methanol
  4. concentrationThe basic fractions were concentrated
  5. customthe crude product was further purified by column chromatography
  6. washeluted with a gradient of EtOAc in hexane
  7. customwas removed by a second ion exchange purification on Isolute SCX-II acidic resin
  8. washeluting with methanol

Quellen und Nachweise

ORD-Eintrag
ord-14a2a0b553454013974030c97d989fce
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367658B2

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