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 2170193노트

반응식

HRID 2170193 반응식
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]

참가 물질

7

반응물 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

생성물 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-sulfonamide수율 15.3%

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-0a50fc9073044e698059b9e3bd0849c4
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09050345B2

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