Dimethylamine, hydrochloride → 6-[3-(4-Chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N,N-dimethyl-nicotinamide

HRID 1514700Notes

Reaction equation

HRID 1514700 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)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.Cl.[CH3:27][NH:28][CH3:29].O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC>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]([N:28]([CH3:29])[CH3:27])=[O:21])=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 10473Dimethylamine, hydrochlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667181326-[3-(4-Chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid

Product 1

HCID 469287676-[3-(4-Chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N,N-dimethyl-nicotinamideYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[3-(4-chloro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (100 mg, 0.28 mmol) and dimethylamine hydrochloride (23.1 mg, 0.28 mmol) in THF (10 mL) were added at 0° C., 1-hydroxybenzotriazole hydrate (43.3 mg, 0.28 mmol), N-ethyldiisopropylamine (170 μL, 0.97 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (54.2 mg, 0.28 mmol). The reaction mixture was stirred at room temperature overnight. The solvent was removed by distillation. The remaining material was purified by chromatography (silica, ethyl acetate:heptane=4:6 to 1:0) to afford the title compound (66 mg, 61%) as a white solid. MS: m/e=446.3 [M+OAc]−.

Workup

  1. customThe solvent was removed by distillation
  2. customThe remaining material was purified by chromatography (silica, ethyl acetate:heptane=4:6 to 1:0)

Sources & evidence

ORD record
ord-5b7ba787f9234562ac4c2e120f6850f7
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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