1,2-Dichloroethane → tert-butyl ((1R,2R,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexyl)carbamate

HRID 705282

反応式

HRID 705282 の反応式
C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.[NH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[C@H:22]1[CH2:27][C@@H:26]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C@H:25]([N:36]=[N+]=[N-])[C@@H:24]([CH3:39])[CH2:23]1.[F:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[C:42]=1[C:48]1[N:53]=[C:52]([C:54](O)=[O:55])[CH:51]=[CH:50][C:49]=1[F:57].[N-]=[N+]=[N-]>CN(C=O)C.O.CC(O)C.[Pd]>[NH2:36][C@@H:25]1[C@@H:24]([CH3:39])[CH2:23][C@@H:22]([C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[NH:15][C:54](=[O:55])[C:52]2[CH:51]=[CH:50][C:49]([F:57])=[C:48]([C:42]3[C:41]([F:40])=[CH:46][CH:45]=[CH:44][C:43]=3[F:47])[N:53]=2)[CH2:27][C@H:26]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]

参加物

10

反応物 5

HCID 111,2-DichloroethaneHCID 33558AzideHCID 181649HOAtHCID 592265526-(2,6-Difluorophenyl)-5-fluoropicolinic acidHCID 86705244(+/-)-tert-butyl ((1R,2R,3 S,5R)-5-(3-aminopyridin-4-yl)-2-azido-3-methyl cyclohexyl)carbamate

生成物 1

HCID 86705240tert-butyl ((1R,2R,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexyl)carbamate収率 35%

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

EDC (2.0 equiv.) and HOAt (2.0 equiv.) was added to a solution of (+/−)-tert-butyl ((1R,2R,3S,5R)-5-(3-aminopyridin-4-yl)-2-azido-3-methyl cyclohexyl)carbamate (1.0 equiv.) and 6-(2,6-difluorophenyl)-5-fluoropicolinic acid (1.5 equiv.) in DMF (0.20 M). The mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, concentrated and purified by ISCO SiO2 chromatography. To a degassed a solution of the azide (1.0 equiv.) in 2-propanol (0.10 M) was added Pd/C (0.2 equiv.). The mixture was stirred under H2 for 48 hrs. Filter the mixture over cetlite and wash the cake with MeOH. Concentrate the filtrate to yield (+/−)-tert-butyl ((1R,2R,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexyl)carbamate in 35% yield). LC/MS (m/z)=556.3 (MH+), Rt=0.64 min.

後処理

  1. extractionextracted with ethyl acetate
  2. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by ISCO SiO2 chromatography
  7. stirringThe mixture was stirred under H2 for 48 hrs
  8. filtrationFilter the mixture over cetlite
  9. washwash the cake with MeOH
  10. concentrationConcentrate the filtrate

出典と根拠

ORDレコード
ord-8c40fa96d840416285b5401361c7355f
出典データセット
uspto-grants-2015_11
特許番号
US09173883B2

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