Potassium Phosphate, Tribasic → HCID 89995494, compound

HRID 1487320Notes

Reaction equation

HRID 1487320 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)=[C:8]([C:24](=[O:26])[NH2:25])[CH:7]=[N:6][N:5]2[CH:27]=1.[CH2:28]([N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1)[CH3:29].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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:24]([C:8]1[CH:7]=[N:6][N:5]2[CH:27]=[C:2]([C:33]3[CH:32]=[N:31][N:30]([CH2:28][CH3:29])[CH:34]=3)[N:3]=[C:4]2[C:9]=1[NH:10][C@H:11]1[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1)(=[O:26])[NH2:25]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 89995496HCID 89995496, compound

Product 1

HCID 89995494HCID 89995494, 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-methylpyrrolidine-1-carboxylate (200 mg, 0.455 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (202 mg, 0.911 mmol), and 2M aq K3PO4 (0.683 ml, 1.366 mmol) in dioxane (2 ml) in a reaction vial was purged with N2 for 2 min, followed by addition of PdCl2(dppf) CH2Cl2 Adduct (1:1) (37.5 mg, 0.046 mmol). The reaction mixture was purged with nitrogen for 1 min, sealed and heated at 100° C. for 120 min. The product 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 column (ISCO 12 g, 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-methylpyrrolidine-1-carboxylate as an off-white solid, 139 mg. ESI-MS (Method A): m/z 455.2 ([M+H]+).

Workup

  1. customvial was purged with N2 for 2 min
  2. customThe reaction mixture was purged with nitrogen for 1 min
  3. customsealed
  4. customThe product mixture was partitioned between EtOAc and water
  5. washThe organic phase was washed with brine
  6. filtrationfiltered through CELITE®
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude product was purified by flash column (ISCO 12 g, 20-80% EtOAc/hexane over 15 min)

Sources & evidence

ORD record
ord-1eccd0eedea4456faaf487fc54c763c6
Source dataset
uspto-grants-2016_08
Patent number
US09428511B2

Reaction notes

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