Chlorosuccinimide → 3-Chloro-4-((1,4-dimethylpiperidin-4-yl)methoxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60269Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][C:5]([CH2:9][O:10][C:11]2[C:19]3[C:18]4[CH:20]=[C:21]([C:24]#[N:25])[N:22]=[CH:23][C:17]=4[NH:16][C:15]=3[N:14]=[CH:13][CH:12]=2)([CH3:8])[CH2:4][CH2:3]1.[Cl:26]N1C(=O)CCC1=O>C(#N)C.C(O)(C)C>[Cl:26][C:12]1[CH:13]=[N:14][C:15]2[NH:16][C:17]3[CH:23]=[N:22][C:21]([C:24]#[N:25])=[CH:20][C:18]=3[C:19]=2[C:11]=1[O:10][CH2:9][C:5]1([CH3:8])[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 4-((1,4-dimethylpiperidin-4-yl)methoxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (50 mg, 0.16 mmol), N-chlorosuccinimide (60 mg, 0.45 mmol) in acetonitrile (0.8 mL) and isopropyl alcohol (0.23 mL) was stirred at 40° C. for 16 hours. The reaction mixture was diluted acetonitrile (1 mL) and the solid was collected by centrifugation, dissolved in dimethylsulfoxide (2 mL), and purified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as a white solid (12 mg, 20%). 1H NMR (500 MHz, d6-DMSO) δ 9.04 (s, 1H), 8.68 (s, 1H), 8.53 (s, 1H), 4.28 (s, 2H), 2.51-2.46 (m, 2H), 2.28 (m, 2H), 2.22 (s, 3H), 1.82 (m, 2H), 1.51 (m, 2H), 1.19 (s, 3H), NH signal not observed. LCMS (Method D): RT=8.445 min, M+H+=370.1.

Workup

customthe solid was collected by centrifugation
dissolutiondissolved in dimethylsulfoxide (2 mL)
custompurified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min]

Sources & evidence

ORD record: ord-581419d4fbf641388095b5e74e330bfd
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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