Sodium Carbonate → N-(7-(6-chloro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468824Notes

Reaction equation

HRID 468824 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[N:24]=[CH:23][C:22](B(O)O)=[C:21]([CH3:28])[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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>[Cl:18][C:19]1[N:24]=[CH:23][C:22]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]4[CH2:17][CH2:16]4)=[O:14])[N:8]=[CH:9]3)=[CH:4][CH:3]=2)=[C:21]([CH3:28])[CH:20]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 441191696-Chloro-4-methylpyridine-3-boronic acidHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 76401541N-(7-(6-chloro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamideYield 84.4%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (300 mg, 1.0 mmol), 6-chloro-4-methylpyridin-3-ylboronic acid (350 mg, 2.1 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (56 mg, 0.08 mmol), and saturated aqueous sodium carbonate (0.5 mL) in acetonitrile (5 mL) was heated under microwave irradiation (Biotage, 200 watts) at 120° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by flash chromatography (silica, 12 g, ISCO, 0-75% ethyl acetate in heptane) to afford the title compound as an off-white solid (285 mg, 80%), which was used in the next step without further purification.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica, 12 g, ISCO, 0-75% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-fcd7a28b8aae49f98b7a77b0ea360421
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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