Trifluoroacetic acid → 7-Methoxy-4-((6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline

HRID 2176525

반응식

HRID 2176525 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[N:7]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[N:35][N:36]([CH:38]3[CH2:43][CH2:42][N:41](C(OC(C)(C)C)=O)[CH2:40][CH2:39]3)[CH:37]=2)O1.C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>CCOC(C)=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.O1CCOCC1>[CH3:24][O:23][C:19]1[CH:18]=[C:17]2[C:22]([C:13]([O:12][CH2:11][C:8]3[N:6]4[N:7]=[C:2]([C:33]5[CH:34]=[N:35][N:36]([CH:38]6[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]6)[CH:37]=5)[CH:3]=[CH:4][C:5]4=[N:10][N:9]=3)=[CH:14][CH:15]=[N:16]2)=[CH:21][CH:20]=1

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinolineHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

생성물 1

HCID 576909647-Methoxy-4-((6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

In a 50 mL sealable flask was charged with PdCl2(dppf)-CH2Cl2 adduct (0.011 g, 0.013 mmol), 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (0.150 g, 0.44 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.18 g, 0.48 mmol), sat NaHCO3 (0.75 ml, >0.97 mmol) and 4 mL dioxane. The vessel was sealed and the mixture heated at 80 C for 22 h. The mixture was allowed to cool to rt and diluted with EtOAc, the organic layer washed with water, sat. NaHCO3, dried over Na2SO4, filtered and evaporated. The residue was dissolved in 5 mL CH2Cl2 and TFA (1.20 ml, 16 mmol) was added. The mixture was stirred at rt for 10 min and evaporated. The residue was taken up into CH2Cl2 and stirred with minimal 2N NaOH for 1 h (ph basic). The mixture was evaporated and purified by prep hplc. The title compound was obtained as an off-white solid. M/Z=457.3 [M+H], calc 456.5076 for C24H24N8O2.

후처리

  1. customThe vessel was sealed
  2. temperaturethe mixture heated at 80 C for 22 h
  3. washthe organic layer washed with water, sat. NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in 5 mL CH2Cl2
  8. customevaporated
  9. stirringstirred with minimal 2N NaOH for 1 h (ph basic)
  10. customThe mixture was evaporated
  11. custompurified by prep hplc

출처 및 근거

ORD 기록
ord-a55de82aa42d43c09c864197129f137d
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09066954B2

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