Sodium Carbonate → HCID 58095188, compound

HRID 2282110Notes

Reaction equation

HRID 2282110 reaction equation
[C:1]([C:3]1[C:4]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])=[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[S:6][C:7]=1I)#[N:2].[F:22][C:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.CCOC(C)=O.C([O-])(O)=O.[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[C:4]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])=[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[S:6][C:7]=1[C:27]1[CH:26]=[CH:25][N:24]=[C:23]([F:22])[CH:28]=1)#[N:2]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 59250036HCID 59250036, compound

Product 1

HCID 58095188HCID 58095188, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of ethyl 4-cyano-3-(2,4-dichlorophenyl)-5-iodothiophene-2-carboxylate (1.81 g, 0.00400 mol), 2-Fluoro-4-pyridinylboronic acid (1.13 g, 0.00801 mol), Tetrakis(triphenylphosphine)palladium(0) (0.231 g, 0.0002 mol) and sodium carbonate (1.27 g, 0.0120 mol) in 1,2-Dimethoxyethane (20 mL) and Water (10 mL) was heated under microwave irradiation at 140° C. for 15 min. The reaction mixture was diluted with EtOAc and sat. NaHCO3. The layers were separated and the aqueous layer was extracted 2× with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated to in vacuo to brown oil. The residue was loaded onto a 24 g Analogix silica gel column and eluted with hexane (3 min) to 50% EtOAc in hexanes (25 min gradient). The appropriate fractions were concentrated to a white solid (1.25 g, 74%). LCMS: (FA) ES+, 421, 423. 1H NMR (400 MHz, d6-DMSO) 8.42 (d, J=5.28 Hz, 1H), 7.65 (td, J=5.27, 1.51, 1.51 Hz, 1H), 7.57 (d, J=2.00 Hz, 1H), 7.45-7.34 (m, 1H), 7.29 (d, J=8.26 Hz, 1H), 4.34-4.17 (m, 1H), 1.21 (t, J=7.14, 7.14 Hz, 1H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted 2× with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to in vacuo to brown oil
  7. washeluted with hexane (3 min) to 50% EtOAc in hexanes (25 min gradient)
  8. concentrationThe appropriate fractions were concentrated to a white solid (1.25 g, 74%)

Sources & evidence

ORD record
ord-860bf1f3d8854041835268bee79181ee
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

Loading…