Water → HCID 68182964, compound

HRID 1615573Notes

Reaction equation

HRID 1615573 reaction equation
C([N:4]1[C@@H:9]([C:10]([O:12]CC)=[O:11])[C@H:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[C:7]2[CH:22]=[C:23](Br)[S:24][C:6]=2[C:5]1=[O:26])C=C.[CH3:27][C:28]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[CH:30][N:29]=1.O1CCOCC1.O.C(=O)([O-])[O-].[Cs+].[Cs+]>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>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C@H:8]2[C@H:9]([C:10]([OH:12])=[O:11])[NH:4][C:5](=[O:26])[C:6]3[S:24][C:23]([C:32]4[CH:31]=[CH:30][N:29]=[C:28]([CH3:27])[CH:33]=4)=[CH:22][C:7]2=3)=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 68183112HCID 68183112, compound

Product 1

HCID 68182964HCID 68182964, compoundYield 96.8%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl rel-(4R,5R)-6-allyl-2-bromo-4-(4-chlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate (505.0 mg, 1.11 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridine (486 mg, 2.22 mmol) in 1,4-dioxane (14.6 mL, 187 mmol) and water (1.9 mL, 110 mmol) were added tetrakis(triphenylphosphine)palladium(0) (64.2 mg, 0.055 mmol) and cesium carbonate (1.08 g, 3.33 mmol). The mixture was stirred at 80° C. for 16 hr. After the reaction was completed, the solvent was evaporated and the obtained residue was purified by column chromatography (SiO2, elution with 0-100% [(60/20/20/20) EA/ACN/MeOH/water)]/EA to give the title compound as a yellow solid (428.7 mg, 73% yield). LCMS: (AA) ES+ , 399/401. 1H NMR (400 MHz, DMSO) δ 8.72 (d, J=6.1 Hz, 1H), 8.45 (d, J=6.6 Hz, 1H), 8.30 (d, J=4.4 Hz, 1H), 8.13 (s, 1H), 8.02 (d, J=8.8 Hz, 1H), 7.43 (t, J=10.0 Hz, 2H), 7.21 (dd, J=24.7, 7.7 Hz, 3H), 4.98-4.59 (m, 1H), 4.32 (d, J=2.9 Hz, 1H), 2.69 (s, 3H).

Workup

  1. customthe solvent was evaporated
  2. customthe obtained residue was purified by column chromatography (
  3. washSiO2, elution with 0-100% [(60/20/20/20) EA/ACN/MeOH/water)]/EA

Sources & evidence

ORD record
ord-d040d27cd7e74f209607ae9a865f4f14
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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