Cesium carbonate → 6-hydroxy-4-oxo-3-[4-(1H-pyrazol-5-yl)phenyl]-7H-thieno[2,3-b]pyridine-5-carbonitrile

HRID 1244132Notes

Reaction equation

I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([OH:17])=[C:14]([C:18]#[N:19])[C:13](=[O:20])[NH:12][C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:35]2[CH:39]=[CH:38][NH:37][N:36]=2)O1>CN(C=O)C.O1CCOCC1.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:17][C:15]1[C:16]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:35]4[CH:39]=[CH:38][NH:37][N:36]=4)=[CH:3][CH:4]=3)=[CH:9][S:10][C:11]=2[NH:12][C:13](=[O:20])[C:14]=1[C:18]#[N:19]

Participants

Conditions

Temperature: 130 °C

Procedure

To a suspension of 3-(4-iodo-phenyl)-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carbonitrile (60 mg, 0.15 mmol) and MgO (18 mg, 0.45 mmol) in 2 mL DMF and 2 mL dioxane, was added Cs2CO3 (0.45 mL, 1M solution in H2O), followed by 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (38 mg, 0.2 mmol), and Pd(PPh3)4 (10 mg, 0.008 mmol). The reaction was heated to 130° C. using microwave reactor for 15 min, filtered, concentrated and purified by reverse phase HPLC to give the titled compound. MS (ESI) m/e 335 (M+H)+; 1H NMR (500 MHz, DMSO-d6): δ 6.61 (s, 1H), 7.00 (s, 1H), 7.43 (d, J=8.42 Hz, 2H), 7.49 (d, J=8.42 Hz, 2H), 8.04 (s, 1H).

Workup

customfor 15 min
filtrationfiltered
concentrationconcentrated
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-4975378635bf4598a60d42cc3fddfcf2
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07119205B2

Reaction notes

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