Water → N-(7-(2-methylprop-1-enyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468755Notes

Reaction equation

HRID 468755 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.[CH3:18][C:19]([CH3:30])=[CH:20]B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O>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.C(OCC)(=O)C>[CH3:20][C:19]([CH3:30])=[CH:18][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

Participants

8

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 151484474,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolaneHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974264N-(7-(2-methylprop-1-enyl)isoquinolin-3-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (121.6 mg, 0.4177 mmol, 2-methyl-1-propenylboronic acid pinacol ester (129 uL, 0.629 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (15.9 mg, 0.0224 mmol), and potassium carbonate (150.5 mg, 1.089 mmol) was added 1,4-dioxane (2 mL, 20 mmol) and water (0.2 mL, 10 mmol). The reaction mixture was stirred at 90° C. for 3 hours. The reaction mixture was then poured into ethyl acetate, which was washed with two portions water, dried with brine and MgSO4, filtered, and evaporated in vacuo to yield 144.5 mg of crude product. 44 mg of this crude material was purified via reverse phase HPLC and lyophilized to yield 28.2 mg N-(7-(2-methylprop-1-enyl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=4.919, M+H=267.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 9.10 (s, 1H), 8.41 (s, 1H), 7.86 (s, 1H), 7.80 (d, J=8.6 Hz, 1H), 7.57 (dd, J=8.6, 1.4 Hz, 1H), 6.41 (s, 1H), 2.12-1.99 (m, 1H), 1.93 (d, J=7.7 Hz, 6H), 0.83 (m, 4H).

Workup

  1. washwas washed with two portions water
  2. dry with materialdried with brine and MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customto yield 144.5 mg of crude product
  6. custom44 mg of this crude material was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-1ce068da9f2b4f8b858036fef60653df
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

Loading…