Sodium Carbonate → 3-Amino-6-(4-(3-(tert-butyldimethylsilyloxy)propyl)phenyl)-N-(pyridin-3-yl)-pyrazine-2-carboxamide

HRID 217772

反応式

HRID 217772 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].C([O-])([O-])=O.[Na+].[Na+].[NH2:48][C:49]1[C:50]([C:56]([NH:58][C:59]2[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=2)=[O:57])=[N:51][C:52](Br)=[CH:53][N:54]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH2:48][C:49]1[C:50]([C:56]([NH:58][C:59]2[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=2)=[O:57])=[N:51][C:52]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=2)=[CH:53][N:54]=1

参加物

9

反応物 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 104021623-Amino-6-bromo-N-pyridin-3-ylpyrazine-2-carboxamideHCID 15342962HCID 15342962、化合物

生成物 1

HCID 666786503-Amino-6-(4-(3-(tert-butyldimethylsilyloxy)propyl)phenyl)-N-(pyridin-3-yl)-pyrazine-2-carboxamide収率 62.3%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of the product of step (ii) (9.84 g, 30 mmol), bis(pinacolato)diboron (11.4 g, 45 mmol), KOAc (9 g, 90 mmol) and Pd(dppf)Cl2 (1 g, 1.5 mmol) in dioxane (200 mL) was stirred and degassed with N2 (×3). The mixture was stirred at 80° C. under a N2 atmosphere for 3 hours. The reaction mixture was cooled to room temperature. Water (25 mL) and Na2CO3 (10 g, 90 mmol) were added to the mixture. The mixture was stirred for 10 minutes before the product of step (v) (7.9 g, 27 mmol) and Pd(dppf)Cl2 (0.5 g, 0.7 mmol) were added. The resulting solution was degassed again with N2 (×3). The reaction mixture was stirred at 90° C. under a N2 atmosphere for additional 10 hours. Na2SO4 was added, filtered and the filtrate concentrated in vacuo. The crude product was purified by column chromatography with PE:EtOAc=5:1 to 3:1 as eluent to afford the subtitle compound (vi) as a yellow solid (7.8 g).

後処理

  1. customdegassed with N2 (×3)
  2. stirringThe mixture was stirred at 80° C. under a N2 atmosphere for 3 hours
  3. additionwere added
  4. customThe resulting solution was degassed again with N2 (×3)
  5. stirringThe reaction mixture was stirred at 90° C. under a N2 atmosphere for additional 10 hours
  6. additionNa2SO4 was added
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. customThe crude product was purified by column chromatography with PE

出典と根拠

ORDレコード
ord-8f06ac597e2842a492e02395d14ac654
出典データセット
uspto-grants-2012_06
特許番号
US08198285B2

関連ノート

読み込み中…