1-((2-Chloro-6-fluorophenyl)methyl)piperazine → 5-Chloro-4-(4-(2-chloro-6-fluorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine

HRID 416713

Reaction equation

[Cl:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[NH2:16][C:17]1[C:22]([N+:23]([O-:25])=[O:24])=[C:21](Cl)[C:20]([Cl:27])=[CH:19][N:18]=1>C(O)(C)C>[Cl:27][C:20]1[C:21]([N:8]2[CH2:7][CH2:6][N:5]([CH2:4][C:3]3[C:11]([F:15])=[CH:12][CH:13]=[CH:14][C:2]=3[Cl:1])[CH2:10][CH2:9]2)=[C:22]([N+:23]([O-:25])=[O:24])[C:17]([NH2:16])=[N:18][CH:19]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of 1-(2-chloro-6-fluorobenzyl)piperazine (0.063 g, 0.28 mmol), isopropanol (4.3 ml), and 2-amino-4,5-dichloro-3-nitropyridine (0.042 g, 0.20 mmol) was heated at 45° C. for 22 h. The reaction mixture was allowed to cool to room temperature, and concentrated in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted first with 30% petroleum ether 60-80° C., and then ethyl acetate. The title compound was obtained as a yellow solid (0.050 g, 62%); 1H-NMR (500 Mz, DMSO-d6) 2.56 (br s, 4H, piperazine N(CH2)2), 3.01 (br s, 4H, piperazine N(CH2)2), 3.66 (s, 2H, NCH2), 6.94 (s, 2H, 2-NH2), 7.23 (t, J=8.91 Hz, 1H) and 7.38 (m, 2H) (ArH), 8.06 (s, 1H, 6-H); LC-MS (ESI, m/z) 4.85 min—400, 402, 404 [(M+H)+, Cl2 isotopic pattern].

Workup

temperatureto cool to room temperature
concentrationconcentrated in vacuo
customThe residue was absorbed on silica gel
washwas eluted first with 30% petroleum ether 60-80° C.

Sources & evidence

ORD record: ord-fe4819e48d10437488fe34d25a56f14f
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Linked notes

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