Water → Methyl 5-(3-aminoisoquinolin-7-yl)-6-methylnicotinate

HRID 468919Notes

Reaction equation

HRID 468919 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH2:19])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.Br[C:22]1[CH:23]=[C:24]([C:29]([O:31][CH3:32])=[O:30])[CH:25]=[N:26][C:27]=1[CH3:28].C(=O)([O-])[O-].[K+].[K+].COCCOC.O>C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[NH2:19][C:14]1[N:15]=[CH:16][C:17]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([C:22]1[C:27]([CH3:28])=[N:26][CH:25]=[C:24]([CH:23]=1)[C:29]([O:31][CH3:32])=[O:30])[CH:18]=2

Participants

8

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 58001778Methyl 5-bromo-6-methylnicotinateHCID 679762687-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine

Product 1

HCID 67975074Methyl 5-(3-aminoisoquinolin-7-yl)-6-methylnicotinateYield 74%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine (337.3 mg; 0.8742 mmol), methyl 5-bromo-6-methyl-pyridine-3-carboxylate (214.2 mg; 0.9311 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (63.3 mg; 0.0894 mmol), potassium carbonate (307.2 mg; 2.223 mmol), 1,2-dimethoxyethane (3.0 mL; 28 mmol), and water (0.3 mL; 20 mmol) was subjected to microwave irradiation at 110° C. for 90 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 189.8 mg (74%) of the title compound. LCMS (ESI): M+H=294.2; 1H NMR (400 MHz, DMSO) δ 8.98 (d, J=1.9 Hz, 1H), 8.88 (s, 1H), 8.10 (d, J=1.9 Hz, 1H), 7.88 (s, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.54 (d, J=8.6 Hz, 1H), 6.67 (s, 1H), 6.03 (s, 2H), 3.90 (s, 3H), 2.57 (s, 3H).

Workup

  1. customirradiation at 110° C. for 90 minutes
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0231f21ea1d9415ca8d11eedb8c12cb8
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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