8-Hydroxyquinoline → HCID 58998405, compound

HRID 1593060Notes

Reaction equation

HRID 1593060 reaction equation
[C:1]([O:5][C:6](=[O:21])[N:7]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[F:19])[C:15](=[O:20])[NH:14][CH:13]=[CH:12]2)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[NH2:22][C:23]1[CH:28]=[CH:27][C:26](I)=[CH:25][N:24]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.CS(C)=O>[C:1]([O:5][C:6](=[O:21])[N:7]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[F:19])[C:15](=[O:20])[N:14]([C:26]1[CH:25]=[N:24][C:23]([NH2:22])=[CH:28][CH:27]=1)[CH:13]=[CH:12]2)[CH3:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 885792-Pyridinamine, 5-iodo-HCID 58998406HCID 58998406, compound2×

Product 1

HCID 58998405HCID 58998405, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
115 °C

Procedure

In a dry flask was combined (7-Fluoro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-methyl-carbamic acid tert-butyl ester (Example 45, compound 10, Scheme B) (102 mg, 0.35 mmol), 2-amino-5-iodopyridine (84 mg, 0.38 mmol, 1.1 eq), copper (I) iodide (7 mg, 0.037 mmol, 0.11 eq), 8-hydroxyquinoline (6 mg, 0.041 mmol, 0.12 eq) and powdered potassium carbonate (58 mg, 0.42 mmol, 1.2 eq). Under Ar atmosphere, dry dimethylsulfoxide (DMSO, 1.5 mL) was added, and the mixture was stirred at 115° C. for 50 hr. The reaction was cooled, concentrated and purified by chromatography (silica, 2-15% isopropyl alcohol/dichloromethane) to give 67 mg (50%) of [2-(6-Amino-pyridin-3-yl)-7-fluoro-1-oxo-1,2-dihydro-isoquinolin-6-yl]-methyl-carbamic acid tert-butyl ester as a grey solid. ES-MS (M+H)+=385. 1H-NMR (DMSO-d) δ (ppm): 1.33 (s, 9), 3.19 (s, 3), 6.25 (br m, NH2), 6.53 (m, 1), 6.64-6.65 (d, 1), 7.37-7.39 (d, 1), 7.44-7.46 (d, 1), 7.77-7.79 (d, 1), 7.87-7.90 (d, 1), 7.95 (m, 1H).

Workup

  1. customIn a dry flask was combined
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. custompurified by chromatography (silica, 2-15% isopropyl alcohol/dichloromethane)

Sources & evidence

ORD record
ord-75fedbe13a8441edb90e2773e6babe28
Source dataset
uspto-grants-2007_11
Patent number
US07294635B2

Reaction notes

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