Hydrogen Bromide → HCID 58365094, compound

HRID 60291Notes

Reaction equation

HRID 60291 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][C:6]([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)([CH3:9])[CH2:5][CH2:4]1)[CH3:2].Br.[OH-].[Na+].Cl>O1CCOCC1>[CH2:1]([N:3]1[CH2:8][CH2:7][C:6]([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)([CH3:9])[CH2:5][CH2:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58365198HCID 58365198, compound

Product 1

HCID 58365094HCID 58365094, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

4-((1-ethyl-4-methylpiperidin-4-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (58 mg, 0.12 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 (13 mg, 30%). 1H NMR (400 MHz, d6-DMSO) δ 8.98 (d, J=0.8, 1H), 8.54 (d, J=5.7, 1H), 8.35 (d, J=0.8, 1H), 7.06 (d, J=5.8, 1H), 4.12 (s, 2H), 2.56 (m, 2H), 2.42-2.25 (m, 4H), 1.75 (m, 2H), 1.54 (m, 2H), 1.19 (s, 3H), 1.08-0.97 (m, 3H). LCMS (Method D): RT=8.49 min, M+H+=450.1.

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-608b684388e94461bdce74af70058d5d
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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