Hydrogen Bromide → HCID 86656043, compound

HRID 60282Notes

Reaction equation

CC1(CO[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)CCCNC1.Br.[OH-:34].[Na+].Cl>O1CCOCC1>[CH3:17][C:18]1([O:34][C:12]2[CH:11]=[CH:10][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]=2)[CH2:10][CH2:11][CH2:12][NH:13][CH2:14]1

Participants

Conditions

Temperature: 75 °C

Procedure

4-((3-methylpiperidin-3-yl)methoxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (52 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 10 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 an off-white solid (11 mg, 31%). 1H NMR (400 MHz, d6-DMSO) δ 12.18 (s, 1H), 8.70 (d, J=0.9, 1 H), 8.51 (d, J=0.9, 1 H), 8.27 (d, J=9.0, 1H), 6.90 (d, J=9.1, 1H), 4.48 (s, 1H), 3.93-3.84 (m, 1H), 3.64 (d, J=13.0, 1H), 3.55-3.40 (m, 2H), 1.79 (m, 1H), 1.67-1.57 (m, 2H), 1.52 (m, 1H), 1.13 (s, 3H). LCMS (Method E): RT=3.73 min, M+H+=308.2.

Workup

customThe cooled reaction mixture
customproducing a cloudy precipitate
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-ed072c2ec8f54dbe9dc461cfe5b005da
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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