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

HRID 879221

Reaction equation

HRID 879221 reaction equation
[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.[C:44]([C:46]1[CH:50]=[CH:49][S:48][CH:47]=1)#[CH:45].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:45]=[C:44]([C:46]4[CH:50]=[CH:49][S:48][CH:47]=4)[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]

Participants

7

Reactant 4

HCID 297MethaneHCID 8471TriethylamineHCID 35484223-EthynylthiopheneHCID 86705273tert-butyl (3R,4S,5S)-4-azido-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methylpiperidin-3-ylcarbamate

Product 1

HCID 86705272tert-butyl (3R,4S,5S)-1-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-5-methyl-4-(4-(thiophen-3-yl)-1H-1,2,3-triazol-1-yl)piperidin-3-ylcarbamateYield 48%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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 (0.4 equiv.), 3-ethynyl thiophene (5.0 equiv.) and triethylamine (1.0 equiv.), in dioxane (0.09 M) to give a black suspension. The pressure tube was sealed and the mixture was stirred with heating to 100° C. overnight. 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)-5-methyl-4-(4-(thiophen-3-yl)-1H-1,2,3-triazol-1-yl)piperidin-3-ylcarbamate in 48% yield. LC/MS (m/z)=691.2 (MH+), Rt=0.98 min.

Workup

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

Sources & evidence

ORD record
ord-cd639356b79d48d4930e0434aea0d359
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Linked notes

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