Potassium Phosphate, Tribasic → 4-Hydroxy-3-(2'-hydroxy-biphenyl-4-yl)-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

HRID 1244168Notes

Reaction equation

HRID 1244168 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[NH:10][C:9]2[S:13][CH:14]=[C:15]([C:16]3[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=3)[C:8]=2[C:7]=1[OH:23])=[O:5])[CH3:2].[OH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC([O-])=O.CC([O-])=O.[Pd+2].O.C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[NH:10][C:9]2[S:13][CH:14]=[C:15]([C:16]3[CH:21]=[CH:20][C:19]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=4[OH:24])=[CH:18][CH:17]=3)[C:8]=2[C:7]=1[OH:23])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 80271Tri-o-tolylphosphineHCID 2773454(2-Hydroxyphenyl)boronic acidHCID 547275683-(4-Bromo-phenyl)-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 546898724-Hydroxy-3-(2'-hydroxy-biphenyl-4-yl)-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-(4-bromo-phenyl)-4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-carboxylic acid ethyl ester (100 mg, 0.25 mmol), 2-hydroxyphenylboronic acid (53 mg, 0.38 mmol), K3PO4 (169 mg, 0.63 mmol), P(o-tolyl)3 (7.7 mg, 2.5×10−5 mol), and Pd(OAc)2 (2.8 mg, 1.3×10−5 mol) was added THF (1.5 mL) and H2O (0.5 mL). The mixture was purged with nitrogen for 15 min., capped, and heated to 80° C. for 1.5 h. The reaction mixture was concentrated under reduced pressure and purified by reverse phase HPLC (0–70% CH3CN in NH4OAc aq.) to give the titled compound. MS (ESI) m/e 430 (M+Na)+, 408 (M+H)+; 406 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 1.28 (t, J=7.12 Hz, 3H), 4.29 (q, J=7.01 Hz, 2H), 6.89 (td, J=7.46, 1.35 Hz, 1H), 6.96 (dd, J=8.14, 1.02 Hz, 1H), 6.99 (s, 1H), 7.17 (m, 1H), 7.30 (dd, J=7.46, 1.70 Hz, 1H), 7.46 (m, 2H), 7.54 (m, 2H), 9.56 (s, 1H), 12.21 (br s, 1H).

Workup

  1. customThe mixture was purged with nitrogen for 15 min.
  2. customcapped
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. custompurified by reverse phase HPLC (0–70% CH3CN in NH4OAc aq.)

Sources & evidence

ORD record
ord-2ebc00be31794bf2b7414bf12f02fbea
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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