Water → 3-[2-[3-Amino-6-(2-methylsulfinylphenyl)pyrazin-2-yl]ethynyl]phenol

HRID 869034Notes

Reaction equation

HRID 869034 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.[CH3:18][S:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O)=[O:20].[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[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]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[S:19]([CH3:18])=[O:20])=[CH:6][N:7]=1

Participants

9

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27735292-(Methylsulfinyl)phenylboronic acidHCID 86667832HCID 86667832, compound

Product 1

HCID 546709433-[2-[3-Amino-6-(2-methylsulfinylphenyl)pyrazin-2-yl]ethynyl]phenolYield 27.7%

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 (72 mg, 0.2482 mmol), (2-methylsulfinylphenyl)boronic acid (54.80 mg, 0.2978 mmol) and K3PO4 (105.4 mg, 0.4964 mmol) were combined in MeCN (2 mL)/water and Pd[P(tBu)3]2 (6.342 mg, 0.01241 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 (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether, dry loaded) and freeze-dried to give the title product as a yellow solid (24 mg, 26% Yield). 1H NMR (400.0 MHz, DMSO) δ 3.34 (s, 3H), 5.15 (d, 1H), 6.88 (dd, 1H), 7.09 (br s, 2H), 7.19 (d, 1H), 7.27 (t, 1H), 7.60-7.69 (m, 2H), 7.89 (d, 1H), 8.17 (d, 1H), 8.60 (s, 1H) and 9.76 (s, 1H) ppm; MS (ES+) 350.1.

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 (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether, dry loaded)
  9. customfreeze-dried

Sources & evidence

ORD record
ord-4f484c0892c246ccbd5e2ff1de847cb5
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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