Nitrogen → HCID 89995499, compound

HRID 1487326Notes

Reaction equation

HRID 1487326 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([CH2:16][CH3:17])[CH2:14][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:12]3)=[C:8]([C:25](=[O:27])[NH2:26])[CH:7]=[N:6][N:5]2[CH:28]=1.[CH2:29]([N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1)[CH3:30].[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>O1CCOCC1.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]([C:8]1[CH:7]=[N:6][N:5]2[CH:28]=[C:2]([C:34]3[CH:33]=[N:32][N:31]([CH2:29][CH3:30])[CH:35]=3)[N:3]=[C:4]2[C:9]=1[NH:10][C@H:11]1[C@@H:15]([CH2:16][CH3:17])[CH2:14][N:13]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:12]1)(=[O:27])[NH2:26]

Participants

7

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 89995497HCID 89995497, compound

Product 1

HCID 89995499HCID 89995499, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (3S,4S)-tert-butyl 3-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-4-ethylpyrrolidine-1-carboxylate (200 mg, 0.441 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (147 mg, 0.662 mmol) in 2M aq K3PO4 (0.662 ml, 1.324 mmol) and dioxane (2 ml) was purged with N2 for 2 min, followed by addition of PdCl2(dppf) CH2Cl2 Adduct (1:1) (36.3 mg, 0.044 mmol). The reaction mixture was purged with nitrogen for 2 min, sealed and heated at 100° C. for 120 min. The reaction mixture was partitioned between EtOAc and water. The organic phase was washed with brine, filtered through CELITE®, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (ISCO 12 g column, 20-80% EtOAc/hexane over 15 min) to afford (3S,4S)-tert-butyl 3-((7-carbamoyl-2-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-8-yl)amino)-4-ethylpyrrolidine-1-carboxylate as an off-white solid.

Workup

  1. customThe reaction mixture was purged with nitrogen for 2 min
  2. customsealed
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. washThe organic phase was washed with brine
  5. filtrationfiltered through CELITE®
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (ISCO 12 g column, 20-80% EtOAc/hexane over 15 min)

Sources & evidence

ORD record
ord-b9ed741cabeb4f60aa332c7db8850a68
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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