3-Amino-1-propanol → 6-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-N-(3-hydroxy-propyl)-nicotinamide

HRID 1911688Notes

Reaction equation

HRID 1911688 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=3)=[CH:11][O:10][N:9]=2)=[CH:4][CH:3]=1.[NH2:24][CH2:25][CH2:26][CH2:27][OH:28].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:24][CH2:25][CH2:26][CH2:27][OH:28])=[O:21])=[CH:17][N:16]=3)=[CH:11][O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 90863-Amino-1-propanolHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 684437696-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid

Product 1

HCID 684446286-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-N-(3-hydroxy-propyl)-nicotinamideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[3-(4-chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid (200 mg, 0.6 mmol) and 3-amino-1-propanol (0.65 mmol) in THF (6 mL) at 0° C. were added 1-hydroxybenzotriazole hydrate (100.8 mg, 0.65 mmol), N-ethyldiisopropylamine (281.7 μl, 1.613 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidazole hydrochloride (126.2 mg, 0.65 mmol). The resulting reaction mixture was stirred overnight at room temperature. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=3:1 to 1:4) afforded the title compound (73 mg, 70%) which was obtained as a white solid. MS: m/e=374.0 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=3:1 to 1:4)

Sources & evidence

ORD record
ord-02dcc2c0f09b4df5ab31ebba21b80440
Source dataset
uspto-grants-2013_12
Patent number
US08604062B2

Reaction notes

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