Hydrogen Bromide → 4-((4-ethyl-1-methylpiperidin-4-yl)methoxy)-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60298Notes

Reaction equation

HRID 60298 reaction equation
[CH2:1]([C:3]1([CH2:10][O:11][C:12]2[C:20]3[C:19]4[CH:21]=[C:22]([C:25]#[N:26])[N:23]=[CH:24][C:18]=4[N:17](COCC[Si](C)(C)C)[C:16]=3[N:15]=[CH:14][CH:13]=2)[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1)[CH3:2].Br.[OH-].[Na+].Cl>O1CCOCC1>[CH2:1]([C:3]1([CH2:10][O:11][C:12]2[C:20]3[C:19]4[CH:21]=[C:22]([C:25]#[N:26])[N:23]=[CH:24][C:18]=4[NH:17][C:16]=3[N:15]=[CH:14][CH:13]=2)[CH2:4][CH2:5][N:6]([CH3:9])[CH2:7][CH2:8]1)[CH3:2]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58365029HCID 58365029, compound

Product 1

HCID 532507014-((4-ethyl-1-methylpiperidin-4-yl)methoxy)-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 40%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

4-((4-ethyl-1-methylpiperidin-4-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (152 mg, 0.32 mmol) was dissolved in 1,4-dioxane (0.5 mL) and then treated with 48% HBr(aq) (0.5 mL) and heated at 75° C. for 15 minutes. The cooled reaction mixture was then basified to pH ˜12 by dropwise addition of 6N sodium hydroxide and then immediately acidified to pH ˜8-9 by dropwise addition of concentrated hydrochloric acid, producing a cloudy precipitate. 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 (44 mg, 40%). 1H NMR (500 MHz, d6-DMSO) δ 8.98 (s, 1H), 8.55 (d, J=5.7, 1 H), 8.32 (s, 1H), 7.12 (d, J=5.8, 1H), 4.18 (s, 2H), 2.37 (m, 4H), 2.19 (s, 3H), 1.75-1.68 (m, 2H), 1.67 (m, 2H), 1.65-1.57 (m, 2H), 0.86 (t, J=7.5, 3 H). LCMS (Method D): RT=7.36 min, M+H+=350.2.

Workup

  1. customThe cooled reaction mixture
  2. customproducing a cloudy precipitate
  3. customThe solid was collected by centrifugation
  4. dissolutiondissolved in dimethylsulfoxide (2 mL)
  5. custompurified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min]

Sources & evidence

ORD record
ord-b6d97bcf4e3e4298bf0c2f1d61206509
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

Loading…