Water → HCID 66749936, compound

HRID 2401740Notes

Reaction equation

HRID 2401740 reaction equation
Br[C:2]1[S:3][C:4]([C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[CH:5][C:6]=1[CH:7]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH2:10][CH2:9][N:8]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].B1([C:40]2[NH:44][N:43]=[CH:42][CH:41]=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[CH:7]([C:6]1[CH:5]=[C:4]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[S:3][C:2]=1[C:40]1[NH:44][N:43]=[CH:42][CH:41]=1)[N:8]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH2:9][CH2:10]2

Participants

7

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 219315393-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66749680HCID 66749680, compound

Product 1

HCID 66749936HCID 66749936, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
95 °C

Procedure

A mixture of tert-butyl 1-(2-bromo-5-pyridin-4-yl-3-thienyl)-6-chloro-3,4-dihydroisoquinoline-2(1H)-carboxylate (72.0 mg, 0.142 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxabolone)-pyrrazole (27.6 mg, 0.142 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (11.7 mg, 0.0142 mmol) and sodium carbonate (29 mg, 0.27 mmol) in 1,2-dimethoxyethane (3.0 mL, 29 mmol) and water (1.0 mL, 56 mmol) was heated at 95° C. for 4.5 h. A LCMS showed the desired product together with unreacted starting material. Additional [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (11.7 mg, 0.0142 mmol) 3-(4,4,5,5-Tetramethyl-1,3,2-dioxabolone)-pyrrazole (56 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol), sodium carbonate (100 mg, 0.9 mmol) and 1,2-dimethoxyethane (3.0 mL, 29 mmol) were added. The mixture was heated at 100° C. for another 4 h. The mixture was dry-loaded onto silica gel and purified by chromatography to afford tert-butyl 6-chloro-1-[2-(1H-pyrazol-5-yl)-5-pyridin-4-yl-3-thienyl]-3,4-dihydroisoquinoline-2(1H)-carboxylate (41 mg, 58%). LCMS AA ES+ 493.2, 495.1.

Sources & evidence

ORD record
ord-20e194e3f5bd4e4a8ab98c998bc58597
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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