Water → HCID 54689825, compound

HRID 1244137Notes

Reaction equation

HRID 1244137 reaction equation
[OH:1][C:2]1[C:3]2[C:13]([C:14]3[S:15][C:16](I)=[C:17]([CH3:19])[CH:18]=3)=[CH:12][S:11][C:4]=2[NH:5][C:6](=[O:10])[C:7]=1[C:8]#[N:9].O.[OH:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CN(C=O)C.CS(C)=O.CO.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>[OH:1][C:2]1[C:3]2[C:13]([C:14]3[S:15][C:16]([C:26]4[CH:27]=[CH:28][C:23]([OH:22])=[CH:24][CH:25]=4)=[C:17]([CH3:19])[CH:18]=3)=[CH:12][S:11][C:4]=2[NH:5][C:6](=[O:10])[C:7]=1[C:8]#[N:9]

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27343604-Hydroxyphenylboronic acidHCID 54689886HCID 54689886, compound

Product 1

HCID 54689825HCID 54689825, compoundYield 54.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To 4-hydroxy-3-(5-iodo-4-methylthien-2-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (200 mg, 0.48 mmol, Example 222) and MgO (58.0 mg, 1.44 mmol) in dioxane (1.25 ml) and DMF (1.25 ml) was added H2O (0.530 ml) and the mixture was stirred for 10 min and then degassed with N2 for 2 min. 4-hydroxyphenylboronic acid (86 mg, 0.62 mmol), Cs2CO3 (344 mg, 1.06 mmol) and Pd(PPh3)4 (28.0 mg, 0.024 mm were added, the vessel flushed with N2, and then stirred at 80° C. for 2 h. The reaction was cooled to rt and overwhelmed with MeOH, filtered and the filtrate was concentrated to give a brown oil. The residue was taken up in DMSO: MeOH (1:1) and purified by reverse phase HPLC to give the title compound (98 mg, 0.26 mmol, 53%) as a light yellow solid MS (ESI) m/z 381.0 (M+H+); 1H NMR (300 MHz, DMSO-d6) δ ppm 7.51 (s, 3H), 7.28 (d, 1H), 6.83 (d, 1H), 6.79 (s, 1H), 4.09 (m, 1H), 2.22 (s, 1H) and 4-hydroxy-3-(4-methylthien-2-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile (Example 217) as a solid.

Workup

  1. customdegassed with N2 for 2 min
  2. customthe vessel flushed with N2
  3. stirringstirred at 80° C. for 2 h
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customto give a brown oil
  7. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-dcb30b84e8f94d1d833db693b57ecd92
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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