Potassium Phosphate, Tribasic → Methyl 4-cyano-3-(4-isoquinolinyl)benzoate

HRID 1909040Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=1.Br[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[N:25][CH:24]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[C:6]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[N:25][CH:24]=2)[CH:5]=1

Participants

Conditions

Temperature: 120 °C

Procedure

The mixture of 4-cyano-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (100 mg, 0.348 mmole), 4-bromo-isoquinoline (80 mg, 0.383 mmole), Pd2(dba)3 (31.9 mg, 0.035 mmole), Sphos (28.6 mg, 0.070 mmole), 2 molar K3PO4 aqueous (0.4 ml, 0.8 mmole) and dioxane (5 ml) was degassed and heated to 120° C. for 40 minutes in microwave. Reaction solution was diluted with water and extracted with EtOAc. EtOAc layer was concentrated. Residue was purified by using silica gel chromatography, eluting with EtOAc/heptane to afford 4-cyano-3-isoquinolin-4-yl-benzoic acid methyl ester (60 mg, 60%). 1H NMR (400 MHz, CD2Cl2) δ 3.88 (s, 3H), 7.45 (d, J=8.03 Hz, 1H), 7.65 (m, 2H), 7.90 (m, 1H), 8.06 (d, J=8.53 Hz, 1H), 8.15 (m, 2H), 8.42 (s, 1H), 9.29 (s, 1H). HR-MS m/z 289.0979 [M+1].

Workup

customwas degassed
customReaction solution
extractionextracted with EtOAc
concentrationEtOAc layer was concentrated
customResidue was purified
washeluting with EtOAc/heptane

Sources & evidence

ORD record: ord-8f6efa6271e44fc7b44438fd435f8fc4
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598217B2

Reaction notes

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