Triethylamine → 4-{4-[2-(Tetrahydro-2H-pyran-4-yloxy)ethoxy]phenyl}isoquinoline-6-carboxamide

HRID 1959949Notes

Reaction equation

HRID 1959949 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14](C3C4C(=CC(C(OCC[Si](C)(C)C)=O)=CC=4)C=CN=3)=[CH:13][CH:12]=2)[CH2:3][CH2:2]1.[F-].C([N+:41]([CH2:50][CH2:51][CH2:52][CH3:53])([CH2:46][CH2:47][CH2:48][CH3:49])CCCC)CCC.[Cl-].[NH4+].Cl.[CH2:57]([N:59]=C=NCCCN(C)C)[CH3:58].O.[OH:69]N1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O.O1CCCC1>[O:1]1[CH2:2][CH2:3][CH:4]([O:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:51]3[C:52]4[C:47](=[CH:48][CH:49]=[C:58]([C:57]([NH2:59])=[O:69])[CH:53]=4)[CH:46]=[N:41][CH:50]=3)=[CH:13][CH:12]=2)[CH2:5][CH2:6]1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724141Tetrabutylammonium FluorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 866619652-(Trimethylsilyl)ethyl [4-[2-(tetrahydro-2H-pyran-4-yloxy)ethoxy]phenyl}isoquinoline-6-carboxylate

Product 1

HCID 469409774-{4-[2-(Tetrahydro-2H-pyran-4-yloxy)ethoxy]phenyl}isoquinoline-6-carboxamideYield 45%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Into tetrahydrofuran (5 ml), 2-(trimethylsilyl)ethyl [4-(2-2-(tetrahydro-2H-pyran-4-yloxy)ethoxy)phenyl]isoquinoline-6-carboxylate (305 mg, 0.62 mmol) synthesized in Example 4 (4a) was dissolved, to which a solution of 1 M tetrabutylammonium fluoride in tetrahydrofuran (1.2 ml, 1.2 mmol) was added. The resulting mixture was stirred at room temperature for two hours and then concentrated under reduced pressure. The residue thus obtained was dissolved in dimethylformamide (10 ml), to which ammonium chloride (660 mg, 12.3 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (590 mg, 3.1 mmol), 1-hydroxy-1H-benzotriazole monohydrate (470 mg, 3.1 mmol), and triethylamine (2.1 ml, 15.1 mmol) were added. The resulting mixture was stirred overnight at room temperature, to which water was added, followed by extraction with dichloromethane three times. The resulting organic layer was collected and washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (ethyl acetate:methanol, 100:0-95:5, V/V) and recrystallized from methanol-ethyl acetate-hexane to give the desired title compound (108 mg, yield 45%).

Workup

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. customThe residue thus obtained
  4. additionwere added
  5. additionwas added
  6. extractionfollowed by extraction with dichloromethane three times
  7. customThe resulting organic layer was collected
  8. washwashed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationThe solvent was distilled off under reduced pressure
  11. customThe residue thus obtained
  12. customwas purified by silica gel column chromatography (ethyl acetate:methanol, 100:0-95:5, V/V)
  13. customrecrystallized from methanol-ethyl acetate-hexane

Sources & evidence

ORD record
ord-060b928b08cb4907a17f344c951ebf94
Source dataset
uspto-grants-2013_04
Patent number
US08410273B2

Reaction notes

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