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 1925142ノート

反応式

HRID 1925142 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-f6b946f311f64229984f78338e1719c5
出典データセット
uspto-grants-2012_05
特許番号
US08178534B2

反応ノート

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