Triethylamine → 1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide

HRID 1023408Notes

Reaction equation

HRID 1023408 reaction equation
[F:1][C:2]1([F:35])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:18]=[C:19]([C:27]5[CH:28]=[N:29][C:30]([O:33]C)=[CH:31][CH:32]=5)[C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][CH:21]=5)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.C(N(CC)CC)C>O1CCOCC1.Cl>[F:35][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:18]=[C:19]([C:27]5[CH:32]=[CH:31][C:30](=[O:33])[NH:29][CH:28]=5)[C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][CH:21]=5)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 577330101-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 577330241-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide (100 mg, 0.210 mmol) was dissolved in a mixture of 1.2 mL of 1,4-dioxane and 0.6 mL of 4M aqueous hydrochloric acid. The solution was heated at 90° C. for 2 hours. The crude reaction mixture was quenched with one equivalent of triethylamine and was then evaporated to dryness. The crude product was partitioned between dichloromethane and water. The organic layer was separated, dried over sodium sulfate, and a portion of the material was purified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane to yield 1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-oxo-1,6-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide as a white solid. ESI-MS m/z calc. 461.1. found 461.9 (M+1)+. Retention time 1.67 minutes.

Workup

  1. customThe crude reaction mixture
  2. customwas then evaporated to dryness
  3. customThe crude product was partitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customa portion of the material was purified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-f546486ef65e41bf8bd3e5e0cae0aa7a
Source dataset
uspto-grants-2014_05
Patent number
US08722704B2

Reaction notes

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