Potassium Hydroxide → N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide

HRID 1502282Notes

Reaction equation

HRID 1502282 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.[O:18]1CCOCC1.[OH-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(CCC)=CC(CCC)=CC=1CCC)(C)(C)C.O>[OH: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

7

Reactant 3

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67975011N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamideYield 76.3%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 866523322-Di-t-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-tri-1-propylbiphenylCatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A round-bottom flask was charged with N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (3.0058 g, 10.324 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.1843 g, 0.1780 mmol), and 2-di-t-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-tri-1-propylbiphenyl (0.2514 g, 0.5229 mmol). The flask was evacuated and backfilled with nitrogen five times and then 1,4-dioxane (10 mL, 200 mmol) and potassium hydroxide (2.413 g, 43.01 mmol) dissolved in water (10 mL, 800 mmol) were added. The reaction mixture was heated at 90° C. under a nitrogen balloon for 2 hours. The reaction mixture was then cooled to room temperature and poured into 150 mL water. The resulting precipitate was filtered, rinsed with water, and dried under vacuum to yield 1.7974 g (76%) of N-(7-hydroxyisoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): M+H=229.2; 1H NMR (400 MHz, DMSO-d6) δ 10.67 (s, 1H), 9.90 (s, 1H), 8.91 (s, 1H), 8.32 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 7.27 (dd, J=8.9, 2.3 Hz, 1H), 7.22 (s, 1H), 2.13-1.95 (m, 1H), 0.91-0.70 (m, 4H).

Workup

  1. customThe flask was evacuated
  2. additionwere added
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. filtrationThe resulting precipitate was filtered
  5. washrinsed with water
  6. customdried under vacuum

Sources & evidence

ORD record
ord-1c35ca03d98d4383b96b6949b8056483
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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