Citric Acid → 6-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carbonyl azide

HRID 1925142노트

반응식

HRID 1925142 반응식
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:25])([F:24])[C:12]3[CH:13]=[CH:14][C:15]4[N:16]([CH:18]=[C:19]([C:21](O)=[O:22])[N:20]=4)[N:17]=3)=[N:9][N:10]=2)[CH:7]=1.C(N(C(C)C)C(C)C)C.[N-:35]=[N+:36]=[N-:37].[Na+].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:25])([F:24])[C:12]3[CH:13]=[CH:14][C:15]4[N:16]([CH:18]=[C:19]([C:21]([N:35]=[N+:36]=[N-:37])=[O:22])[N:20]=4)[N:17]=3)=[N:9][N:10]=2)[CH:7]=1

참가 물질

8

반응물 5

HCID 311Citric AcidHCID 33557Sodium AzideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 592331396-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylic acid

생성물 1

HCID 866398206-((6-Bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carbonyl azide수율 92%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a stirred solution of 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carboxylic acid (3.5 g, 8.55 mmol), N-ethyl-N-isopropylpropan-2-amine (6.63 g, 51.3 mmol) and sodium azide (5.56 g, 86 mmol) in anhydrous DMF (60 mL), PyBOP (5.34 g, 10.27 mmol) was added in portions at ambient temperature over 5 min. The reaction was stirred for an additional 30 min and diluted with EtOAc (200 mL). The reaction was then poured into a 10% aqueous citric acid (200 mL), and the organic phase was separated and washed with citric acid solution (2×100 mL), saturated NaHCO3 (3×100 mL), and saturated NaCl solution. The aqueous phases were back extracted with EtOAc (200 mL) and the organic phases were combined, dried with MgSO4, filtered, and concentrated to dryness via rotary evaporation. The resulting residue was triturated in 1:1 Et2O/hexane, and the solid was collected by filtration and dried in vacuum over P2O5 to provide the title compound, 6-((6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)difluoromethyl)imidazo[1,2-b]pyridazine-2-carbonyl azide 45K (3.2 g, 7.37 mmol, 92%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (dd, J=9.85, 1.77 Hz, 1 H) 7.88 (d, J=9.60 Hz, 1 H) 8.00-8.05 (m, 1 H) 8.56 (d, J=9.60 Hz, 1 H) 8.98 (s, 1 H) 9.14 (s, 1 H). ESI-MS:m/z 434.0 (M+H)+. ESI-MS:m/z 406.0 (M+H)+.

후처리

  1. customthe organic phase was separated
  2. washwashed with citric acid solution (2×100 mL), saturated NaHCO3 (3×100 mL), and saturated NaCl solution
  3. extractionThe aqueous phases were back extracted with EtOAc (200 mL)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness via rotary evaporation
  7. customThe resulting residue was triturated in 1:1 Et2O/hexane
  8. filtrationthe solid was collected by filtration
  9. dry with materialdried in vacuum over P2O5

출처 및 근거

ORD 기록
ord-f6b946f311f64229984f78338e1719c5
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178534B2

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