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

HRID 2170193ノート

反応式

HRID 2170193 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]([O:48][CH:49]([CH3:51])[CH3:50])=[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]([O:48][CH:49]([CH3:51])[CH3:50])=[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:32])=[O:31])([CH3:28])([CH3:27])[CH3:26]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 90386130N-(tert-butyl)-2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamideHCID 903861572-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

生成物 1

HCID 90386266N-(tert-Butyl)-2-isopropoxy-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide収率 15.3%

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

A solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (50.0 mg, 0.149 mmol), N-(tert-butyl)-2-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (89.0 mg, 0.223 mmol), K2CO3 (62.0 mg, 0.447 mmol) in 1,4-dioxane (20 mL) and water (6 mL) was purged with nitrogen gas for 10 min. PdCl2(dppf)-CH2Cl2 (6.08 mg, 7.45 mol) was added and the reaction mixture purged with nitrogen gas for further 5 min then heated to 100° C. for 12 h. The cooled reaction mixture was filtered through the CELITE® and washed with ethyl acetate (20 mL). The filtrate was washed with brine solution (10 mL). The organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure to give a residue that was purified by preparative HPLC (Condition B-91 as described in general methods) to give N-(tert-butyl)-2-isopropoxy-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (13.0 mg, 15.1%) as a pale yellow solid. LCMS Condition B-79: retention time 2.39 min, [M+1]=572.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.15 (s, 9H), 1.41 (d, J=6.5 Hz, 6H), 4.88 (d, J=5.0 Hz, 2H), 5.13 (quintet, J=6.7 Hz, 1H), 6.78 (d, J=2.5 Hz, 1H), 6.89 (s, 1H), 7.28 (t, J=5.5 Hz, 2H), 7.42-7.49 (m, 2H), 7.50-7.62 (m, 4H), 7.74-7.81 (m, 1H), 7.92 (d, J=2.5 Hz, 1H), 8.40-8.45 (m, 1H), 8.66 (d, J=2.5 Hz, 1H), 8.75 (d, J=2.5 Hz, 1H).

後処理

  1. customthe reaction mixture purged with nitrogen gas for further 5 min
  2. customThe cooled reaction mixture
  3. filtrationwas filtered through the CELITE®
  4. washwashed with ethyl acetate (20 mL)
  5. washThe filtrate was washed with brine solution (10 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a residue that
  10. customwas purified by preparative HPLC (Condition B-91 as described in general methods)

出典と根拠

ORDレコード
ord-0a50fc9073044e698059b9e3bd0849c4
出典データセット
uspto-grants-2015_06
特許番号
US09050345B2

反応ノート

読み込み中…