Triethylamine → Prucalopride hydrochloride

HRID 382316Notes

Reaction equation

[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([NH:13][CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:12])=[CH:4][C:3]=1[Cl:20].Cl[CH2:22][CH2:23][CH2:24][O:25][CH3:26].C(N(CC)CC)C>CN(C)C=O>[ClH:20].[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([CH2:22][CH2:23][CH2:24][O:25][CH3:26])[CH2:16][CH2:15]2)=[O:12])=[CH:4][C:3]=1[Cl:20]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-amino-5-chloro-2,3-dihydro-N-(4-piperidinyl)-7-benzofurancarboxamide(0.01 mol), 1-chloro-3-methoxypropane (0.012 mol), N,N-diethylethanamine (2.1 ml) and KI (catalytic amount) in N,N-dimethylformamide (75 ml) was stirred overnight at 50° C. The reaction mixture was cooled. The solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CHCl3m/(CH3OH/NH3)97/3). The pure fractions were collected and the solvent was evaporated. The residue was dissolved in 2-propanol and converted into the hydrochloric acid salt (1:1) with HCl/2-propanol. The precipitate was filtered off and dried (vacuum; 80° C.), yielding 1.40 g (35%) of 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide monohydrochloride (comp. 1).

Workup

temperatureThe reaction mixture was cooled
customThe solvent was evaporated
customThe residue was purified by column chromatography over silica gel (eluent: CHCl3m/(CH3OH/NH3)97/3)
customThe pure fractions were collected
customthe solvent was evaporated
dissolutionThe residue was dissolved in 2-propanol
filtrationThe precipitate was filtered off
customdried (vacuum; 80° C.)

Sources & evidence

ORD record: ord-13381721ca2848dd82d8da328a37a859
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06310077B1

Reaction notes

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