Hydrochloric Acid → 3-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxyamine

HRID 1977948Notes

Reaction equation

HRID 1977948 reaction equation
[CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:34]=[C:35]([CH3:37])[CH:36]=3)[O:18][CH2:19][CH2:20][CH2:21][O:22][N:23]3C(=O)C4=CC=CC=C4C3=O)(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[BH4-].[Na+].Cl.[OH-].[Na+]>C(O)C.O.O1CCCC1>[CH:1]1[C:10]2[C:5](=[C:6]([S:11]([O:14][C:15]3[CH:16]=[C:17]([CH:34]=[C:35]([CH3:37])[CH:36]=3)[O:18][CH2:19][CH2:20][CH2:21][O:22][NH2:23])(=[O:13])=[O:12])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 22722554n-[3-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxy]phthalimide

Product 1

HCID 227226933-[3-(5-Isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxyamineYield 26%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[3-[3-(5-isoquinolinylsulfonyloxy)-5-methylphenoxy]propoxy]phthalimide (570 mg, 1.1 mmol), as prepared in the preceding step, in ethanol (20 mL), tetrahydrofuran (10 mL), and water (10 mL) was added sodium borohydride (230 mg, 6.0 mmol). The reaction mixture was stirred at ambient temperature overnight. The mixture was acidified (pH 1-2) with 2 N HCl and heated at 50° C. for 2 hours. After cooling to room temperature, 2 N NaOH was added to adjust the pH to 8-9. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with brine (50 mL) and dried over Na2SO4. After removing the solvent, the residue was purified by flash column chromatography (ethyl acetate) to give the title compound as a colorless oil (110 mg, 26%). 1H-NMR (300 MHz, CDCl3) δ9.42 (s, 1H), 8.81 (d, J=6.1 Hz, 1H), 8.54 (d, J=6.1 Hz, 1H), 8.33 (m, 2H), 7.67 (t, J=7.8 Hz, 1H), 6.55 (s, 1H), 6.28 (s, 1H), 6.23 (s, 1H), 3.81 (t, J=6.3 Hz, 2H), 3.74 (t, J=6.1 Hz, 2H), 2.15 (s, 3H), 1.94 (m, 2H). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C19H20N2O5S: 389.1 (M+H), 411.1 (M+Na). Found: 389.3, 411.1.

Workup

  1. temperatureheated at 50° C. for 2 hours
  2. temperatureAfter cooling to room temperature
  3. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic extracts were washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. customAfter removing the solvent
  7. customthe residue was purified by flash column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-5089bb5ef1714d3ba62f892ba588b957
Source dataset
uspto-grants-2001_05
Patent number
US06235778B1

Reaction notes

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