Potassium Carbonate → N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

HRID 2170187ノート

反応式

HRID 2170187 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[C:5]2=[C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:17]=[CH:18][N:4]2[N:3]=1.[C:25]([NH:29][S:30]([C:33]1[C:34]([CH:48]([F:50])[F:49])=[N:35][CH:36]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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].C(Cl)Cl>[C:25]([NH:29][S:30]([C:33]1[C:34]([CH:48]([F:49])[F:50])=[N:35][CH:36]=[C:37]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)[C:5]3=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:17]=[CH:18][N:4]3[N:3]=2)[CH:38]=1)(=[O:31])=[O:32])([CH3:28])([CH3:26])[CH3:27]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 903861572-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 90386255N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide

生成物 1

HCID 90386127N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide収率 71.5%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.500 g, 1.49 mmol) and N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.697 g, 1.79 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added K2CO3 (0.412 g, 2.98 mmol). The reaction mixture was purged with nitrogen gas for 10 min. Then PdCl2(dppf)-CH2Cl2 (0.122 g, 0.149 mmol) was added and heated at 100° C. for 1 h in micro wave. The reaction mixture was allowed to cool to ambient temperature. The reaction mixture was filtered through CELITE® bed and the bed was washed with EtOAc (2×50 mL). The filtrate was diluted with water (50 mL) and extracted with EtOAc (100 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes) to obtain N-(tert-butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.600 g, 71.5% yield) as a pale yellow solid. LCMS Condition B-83: retention time 1.84 min, [M+1]=564.0. 1H NMR (400 MHz, CD3OD) δ ppm 1.26 (s, 9H), 4.94 (s, 2H), 6.81 (d, J=2.8 Hz, 1H), 7.27-7.31 (m, 1H), 7.44-7.55 (m, 3H), 7.59-7.63 (m, 4H), 7.77-7.82 (m, 2H), 8.43 (d, J=4.4 Hz, 1H), 9.19 (dd, J=2.0 Hz, J=1.2 Hz, 1H), 9.64 (d, J=2.0 Hz, 1H).

後処理

  1. customThe reaction mixture was purged with nitrogen gas for 10 min
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered through CELITE® bed
  4. washthe bed was washed with EtOAc (2×50 mL)
  5. additionThe filtrate was diluted with water (50 mL)
  6. extractionextracted with EtOAc (100 mL)
  7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-c368bbf66cae495e96b4723231998622
出典データセット
uspto-grants-2015_06
特許番号
US09050345B2

反応ノート

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