Water → 5-[5-Amino-6-[2-(3-hydroxyphenyl)ethynyl]pyrazin-2-yl]-1-isopropyl-pyridin-2-one

HRID 869036Notes

Reaction equation

HRID 869036 reaction equation
[NH2:1][C:2]1[C:3]([C:9]#[C:10][C:11]2[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=2)=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH:18]([N:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:22]1=[O:36])([CH3:20])[CH3:19].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>CC#N.CCOC(C)=O.Cl.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:25]2[CH:24]=[CH:23][C:22](=[O:36])[N:21]([CH:18]([CH3:20])[CH3:19])[CH:26]=2)=[N:4][C:3]=1[C:9]#[C:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=1

Participants

9

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 580703861-Isopropyl-6-oxo-1,6-dihydropyridine-3-boronic Acid Pinacol EsterHCID 86667832HCID 86667832, compound

Product 1

HCID 546708455-[5-Amino-6-[2-(3-hydroxyphenyl)ethynyl]pyrazin-2-yl]-1-isopropyl-pyridin-2-oneYield 21.1%

Reagents, catalysts & solvents 4

HCID 178418851HCID 178418851, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3-[2-(3-Amino-6-bromo-pyrazin-2-yl)ethynyl]phenol (100 mg, 0.3447 mmol), 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (108.8 mg, 0.4136 mmol) and K3PO4 (146.3 mg, 0.6894 mmol) were combined in MeCN (2 mL)/water (0.5 mL) and Pd[P(tBu)3]2 (8.811 mg, 0.01724 mmol) was added. The reaction was heated at 60° C. for 15 hours. The reaction was cooled to ambient temperature and diluted with EtOAc and 1M HCl. The layers were separated and the aqueous layer extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (VARIAN 971-FP™, 8 g column, eluting with 0 to 10% MeOH/DCM, dry loaded) to give the title compound as a yellow solid (25.2 mg, 21% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.38 (d, 6H), 5.11 (sept, 1H), 6.49 (d, 1H), 6.77 (s, 2H), 6.87 (dd, 1H), 7.12 (s, 1H), 7.18 (d, 1H), 7.25 (t, 1H), 7.99 (dd, 1H), 8.20 (d, 1H), 8.55 (s, 1H) and 9.74 (s, 1H) ppm; MS (ES+) 347.1.

Workup

  1. additionwas added
  2. temperatureThe reaction was cooled to ambient temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with EtOAc (×3)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (VARIAN 971-FP™, 8 g column, eluting with 0 to 10% MeOH/DCM, dry loaded)

Sources & evidence

ORD record
ord-e9e9dc4c9dd74c29a9032201508e68a0
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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