Hydrogen Bromide → HCID 58365077, compound

HRID 60295Notes

Reaction equation

HRID 60295 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][CH2:6][C@@H:5]([O:9][C:10]2[C:18]3[C:17]4[CH:19]=[C:20]([C:23]#[N:24])[N:21]=[CH:22][C:16]=4[N:15](COCC[Si](C)(C)C)[C:14]=3[N:13]=[CH:12][CH:11]=2)[CH2:4]1)[CH3:2].Br.[OH-].[Na+].Cl>O1CCOCC1>[CH2:1]([N:3]1[CH2:8][CH2:7][CH2:6][C@@H:5]([O:9][C:10]2[C:18]3[C:17]4[CH:19]=[C:20]([C:23]#[N:24])[N:21]=[CH:22][C:16]=4[NH:15][C:14]=3[N:13]=[CH:12][CH:11]=2)[CH2:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58365227HCID 58365227, compound

Product 1

HCID 58365077HCID 58365077, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

(R)-4-(1-ethylpiperidin-3-oxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (46 mg, 0.10 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 (12 mg, 37%). 1H NMR (400 MHz, d6-DMSO) δ 12.78 (s, 1H), 8.96 (d, J=0.9, 1H), 8.54-8.51 (d, J=5.9, 1H), 8.50 (d, J=0.9, 1H), 7.11 (d, J=5.9, 1H), 4.93-4.83 (m, 1H), 2.98 (d, J=8.9, 1 H), 2.61 (m, 1H), 2.52 (m, 2H), 2.44 (q, J=7.2, 2H), 2.26 (t, J=8.8, 1H), 2.07 (m, 1H), 1.86-1.75 (m, 1H), 1.66 (m, 2H), 1.04 (t, J=7.1, 3H). LCMS (Method E): RT=7.33 min, M+H+=322.1.

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-b7d707bfb3584eb6a5ee29479fa1e950
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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