Sodium Carbonate → 5-Cyclopropyl-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-furo[2,3-b]pyridine-3-carboxylic acid methylamide

HRID 2190150

Reaction equation

HRID 2190150 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][C:10]([N:15]([S:17]([CH3:20])(=[O:19])=[O:18])[CH3:16])=[C:11](I)[CH:12]=2)[O:7][C:6]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:4].CO[C:30]1C=CC=C(OC)[C:35]=1[C:36]1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][NH:2][C:3]([C:5]1[C:13]2[C:8](=[N:9][C:10]([N:15]([S:17]([CH3:20])(=[O:19])=[O:18])[CH3:16])=[C:11]([CH:36]3[CH2:35][CH2:30]3)[CH:12]=2)[O:7][C:6]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 545750872-(4-fluorophenyl)-5-iodo-N-methyl-6-(N-methylmethylsulfonamido)furo[2,3-b]pyridine-3-carboxamide

Product 1

HCID 545759365-Cyclopropyl-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-furo[2,3-b]pyridine-3-carboxylic acid methylamideYield 516.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
120 °C

Procedure

To 2-(4-Fluoro-phenyl)-5-iodo-6-(methanesulfonyl-methyl-amino)-furo[2,3-b]pyridine-3-carboxylic acid methylamide (7 mg, 0.014 mmol), is added a premixed solution of SPhos (0.571 mg, 1.391 μmol), palladium acetate (0.125 mg, 0.556 μmol) in toluene (0.5 ml) andcyclopropylboronic acid (5.97 mg, 0.070 mmol) premixed with sodium carbonate (0.035 ml, 0.070 mmol). The reaction mixture is heated under microwave irradiation at 120° C. for 10 min. LCMS indicates predominant conversion to product. The toluene layer is transferred to a vial, and the aqueous layer is extracted with toluene and added to the vial. The toluene is removed in vacuo, and the residue is dissolved in DMF, filtered and purified by HPLC to afford 5-Cyclopropyl-2-(4-fluoro-phenyl)-6-(methanesulfonyl-methyl-amino)-furo[2,3-b]pyridine-3-carboxylic acid methylamide (3 mg, 7.19 μmol, 51.7% yield). MS (ESI) m/z 503.9 (M+1). 1H NMR (400 MHz, CD3CN) δ ppm 8.05-8.01 (m, 2H), 7.73 (s, 1H), 7.32-7.27 (m, 2H), 6.82 (br s, 1H), 3.30 (s, 3H), 3.23 (s, 3H), 2.92-2.90 (d, 3H), 2.43-2.38 (m, 1H), 1.12-1.07 (m, 2H), 0.84-0.80 (m, 2H)

Workup

  1. extractionis extracted with toluene
  2. additionadded to the vial
  3. customThe toluene is removed in vacuo
  4. dissolutionthe residue is dissolved in DMF
  5. filtrationfiltered
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-33ffd9e559e84a78ab7cd58a495baab7
Source dataset
uspto-grants-2012_12
Patent number
US08324239B2

Linked notes

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