Methane → tert-butyl (3R,4S,5S)-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-4-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)-5-methylpiperidin-3-ylcarbamate

HRID 879223

Reaktionsgleichung

Reaktionsgleichung von HRID 879223
[N:1]([C@H:4]1[C@@H:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[NH:17][C:18](=[O:34])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]3[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=3[F:33])[N:20]=2)[CH2:6][C@H:5]1[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[N+:2]=[N-:3].C.[CH3:44][O:45][CH2:46][C:47]#[CH:48].C(N(CC)CC)C>O1CCOCC1.[Cu]>[F:32][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([F:33])[C:26]=1[C:21]1[N:20]=[C:19]([C:18]([NH:17][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:11]=2[N:7]2[CH2:8][C@H:9]([CH3:10])[C@H:4]([N:1]3[CH:48]=[C:47]([CH2:46][O:45][CH3:44])[N:3]=[N:2]3)[C@H:5]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:6]2)=[O:34])[CH:24]=[CH:23][C:22]=1[F:25]

Komponenten

7

Edukt 4

HCID 297MethaneHCID 8471TriethylamineHCID 693933-MethoxypropyneHCID 86705273tert-butyl (3R,4S,5S)-4-azido-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-ylcarbamate

Produkt 1

HCID 86705275tert-butyl (3R,4S,5S)-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-4-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)-5-methylpiperidin-3-ylcarbamateAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23978CopperKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

In a high pressure vial was added tert-butyl (3R,4S,5S)-4-azido-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-ylcarbamate (1.0 equiv.), copper in charcoal (0.2 equiv.), 3-methoxyprop-1-yne (1.5 equiv.) and triethylamine (1.5 equiv.), in dioxane (0.20 M) to give a black suspension. The pressure tube was sealed and the mixture was stirred with heating to 70° C. for 16 hrs. The reaction was cooled to RT, filtered through celite, concentrated to yield tert-butyl (3R,4S,5S)-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-4-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)-5-methylpiperidin-3-ylcarbamate in 95% yield. LC/MS (m/z)=653.2 (MH+), Rt=0.86 min.

Aufarbeitung

  1. customThe pressure tube was sealed
  2. temperatureThe reaction was cooled to RT
  3. filtrationfiltered through celite
  4. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-7c977278ec5245f4a707e9d8282e1b3d
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987457B2

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