4-Methoxybenzylamine → 3-[(1-Amino-5-isoquinolyl)oxy]propylamine hydrochloride

HRID 10502

Reaction equation

HRID 10502 reaction equation
C(OC([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][N:17]=[C:18]2[Cl:23])=O)(C)(C)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.COC1C=CC(C[NH2:52])=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[ClH:23].[NH2:52][C:18]1[C:19]2[C:14](=[C:13]([O:12][CH2:11][CH2:10][CH2:9][NH2:8])[CH:22]=[CH:21][CH:20]=2)[CH:15]=[CH:16][N:17]=1

Participants

8

Reactant 4

HCID 754524-MethoxybenzylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 21979957N-(tert-butoxycarbonyl)-3-[(1-chloro-5-isoquinolyl)oxy]propylamine2×HCID 23676156Sodium t-butoxide

Product 1

HCID 219798583-[(1-Amino-5-isoquinolyl)oxy]propylamine hydrochloride

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

The title compound was synthesized from Intermediate 18 according to the method described in a reference (Buchwald, S. L., J. Org. Chem., 65, 1158 (2000)). That is, a suspension of Intermediate 18 (674 mg), tris (dibenzylideneacetone)dipalladium(0) (92 mg, Aldrich), 2-(di-tert-butylphosphino)biphenyl (119 mg, Strem Chemicals), 4-methoxybenzylamine (329 mg, Tokyo Kasei Kogyo) and sodium tert-butoxide (269 mg, Tokyo Kasei Kogyo) in toluene (5 ml) was stirred with heating at 80° C. under nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature and added with ethyl acetate (5 ml). The insoluble matters were removed by filtration through Celite. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (525 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe insoluble matters were removed by filtration through Celite
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-2e01521f8a6a49748b5268aa0846e201
Source dataset
uspto-grants-2006_08
Patent number
US07094789B2

Linked notes

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