Potassium Phosphate, Tribasic → HCID 68292155, compound

HRID 1507960Notes

Reaction equation

HRID 1507960 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][OH:13])=[C:8]([C:18]([NH2:20])=[O:19])[CH:7]=[N:6][N:5]2[CH:21]=1.[CH3:22][N:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)[CH3:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:22][N:23]([CH3:24])[C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[C:4]3[C:9]([NH:10][C@@H:11]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:12][OH:13])=[C:8]([C:18]([NH2:20])=[O:19])[CH:7]=[N:6][N:5]3[CH:21]=2)[CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27625273-(Dimethylamino)benzeneboronic acidHCID 68349473HCID 68349473, compound

Product 1

HCID 68292155HCID 68292155, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-6-bromo-4-(1-hydroxy-4-methylpentan-2-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (23 mg, 0.070 mmol), 3-(N,N-dimethylamino)phenyl boronic acid (16 mg, 0.1 mmol), palladium (II) acetate (1.46 mg, 0.0065 mmol), potassium phosphate, tribasic, 2M (0.1 mL, 0.2 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbyphenyl (6.2 mg, 0.013 mmol) in dioxane (Volume: 0.65 mL) was heated to 90° C. overnight. The reaction mixture was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Gradient: 20-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound (3.8 mg, 15% yield). MS (ES+) m/z: 396.1 (M+H); LC retention time: 1.83 min (analytical HPLC Method B).

Workup

  1. customThe reaction mixture was purified via preparative LC/MS with the following conditions
  2. customa 5-minute hold
  3. additionFractions containing the desired product
  4. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-a2763d2e5b1948bfbdbbc2620b7a0bb9
Source dataset
uspto-grants-2015_12
Patent number
US09221826B2

Reaction notes

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