Water → HCID 66749680, compound

HRID 2401739Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([C:12]1[CH:16]=[C:15](Br)[S:14][C:13]=1[Br:18])[N:7]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:6][CH2:5]2.[N:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>>[Br:18][C:13]1[S:14][C:15]([C:29]2[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=2)=[CH:16][C:12]=1[CH:8]1[C:9]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:11][CH:10]=2)[CH2:5][CH2:6][N:7]1[C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20]

Participants

Reactant 5

HCID 962Water

HCID 10796Cesium carbonate

HCID 312751,4-Dioxane

HCID 2734379(Pyridin-4-yl)boronic acid

HCID 66749673HCID 66749673, compound

Product 1

HCID 66749680HCID 66749680, compoundYield 41%

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl 6-chloro-1-(2,5-dibromo-3-thienyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (177.0 mg, 0.3486 mmol), pyridine-4-boronic acid (51.43 mg, 0.4184 mmol) tetrakis(triphenylphosphine)palladium(0) (20.1 mg, 0.0174 mmol) and cesium carbonate (0.341 g, 1.04 mmol) in 1,4-dioxane (6.0 mL, 77 mmol) and water (2.0 mL, 110 mmol) was degassed and heated at 100° C. for 1 h. The mixture was extracted with EtOAc. The organic layer was separated and washed with water. The organic layer was dried and evaporated to leave a residue which was purified by chromatography to afford tert-butyl 1-(2-bromo-5-pyridin-4-yl-3-thienyl)-6-chloro-3,4-dihydroisoquinoline-2(1H)-carboxylate as a white solid (72 mg, 41%). LCMS AA ES+ 505.1, 507.1

Workup

customwas degassed
extractionThe mixture was extracted with EtOAc
customThe organic layer was separated
washwashed with water
customThe organic layer was dried
customevaporated
customto leave a residue which
customwas purified by chromatography

Sources & evidence

ORD record: ord-39ef5f02d7c7453089e890c205f6cb5e
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796268B2

Reaction notes

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