Potassium Phosphate, Tribasic → 5-(6-Methyl-2,3-dihydrobenzo[3,4-b]furan-5-yl)-2-pyridylamine

HRID 874655Notes

Reaction equation

HRID 874655 reaction equation
Br[C:2]1[C:10]([CH3:11])=[CH:9][C:5]2[O:6][CH2:7][CH2:8][C:4]=2[CH:3]=1.FC1(F)OC2C=C(C)C(C3N=C[C:25]([NH:28][C:29](=O)[C:30]4[CH:35]=[CH:34]C=CC=4F)=[N:26]C=3)=CC=2O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.O1CCOCC1.O>[CH3:11][C:10]1[C:2]([C:30]2[CH:35]=[CH:34][C:25]([NH2:26])=[N:28][CH:29]=2)=[CH:3][C:4]2[CH2:8][CH2:7][O:6][C:5]=2[CH:9]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 225923875-Bromo-6-methyl-2,3-dihydrobenzo[b]furanHCID 58486754N-(5-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2-fluorobenzamide

Product 1

HCID 584873695-(6-Methyl-2,3-dihydrobenzo[3,4-b]furan-5-yl)-2-pyridylamineYield 63%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-bromo-6-methyl-2,3-dihydrobenzo[b]furan (160) (350 mg, purity ca 40%, 0.66 mmol), 2-aminopyridine-5-boronic acid pinacol ester (11) (360 mg, 1.6 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (113 mg, 5% mol), and K3PO4 (348 mg, 1.6 mmol) in 2 ml ACN, 2 ml dioxane, 1 ml H2O was bubbled with argon before heated at 85° C. for 4 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine. Org. phase was dried over Na2SO4, concentrated and then subjected to prep HPLC purification to give 94 mg 5-(6-methyl-2,3-dihydrobenzo[3,4-b]furan-5-yl)-2-pyridylamine (161) (yield: 63%, purity>95%) as light yellow solid.

Workup

  1. customwas bubbled with argon
  2. temperatureAfter cooling down to r.t.
  3. washwashed with aq. NaHCO3 and brine
  4. dry with materialphase was dried over Na2SO4
  5. concentrationconcentrated
  6. customHPLC purification

Sources & evidence

ORD record
ord-a0332b33f14740dfb74709a40d74bdc6
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

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