Hydrogen Bromide → HCID 53250700, compound

HRID 60293Notes

Reaction equation

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

Participants

Conditions

Temperature: 75 °C

Procedure

(R)-4-(1-methylpiperidin-3-yloxy)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (93 mg, 0.21 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 (18 mg, 27%). 1H NMR (400 MHz, d6-DMSO) δ 12.74 (s, 1H), 8.96 (d, J=0.8, 1H), 8.52 (d, J=5.8, 1H), 8.46 (d, J=0.9, 1H), 7.10 (d, J=5.9, 1H), 4.93-4.82 (m, 1H), 2.93 (m, 1H), 2.57-2.51 (m, 1H), 2.44 (m, 1H), 2.24 (s, 3H), 2.19 (m, 1H), 2.08 (m, 1H), 1.83 (m, 1H), 1.68 (m, 2H). LCMS (Method D): RT=7.08 min, M+H+=308.1.

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-346c7d2d99eb42f49cd0299f8f8ece26
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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