Hydrogen Bromide → HCID 58365138, compound

HRID 60312Notes

Reaction equation

[F:1][C:2]([F:34])([F:33])[CH2:3][NH:4][C@H:5]1[CH2:9][CH2:8][N:7]([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)[CH2:6]1.Br.[OH-].[Na+].Cl>O1CCOCC1>[F:34][C:2]([F:1])([F:33])[CH2:3][NH:4][C@H:5]1[CH2:9][CH2:8][N:7]([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)[CH2:6]1

Participants

Conditions

Temperature: 60 °C

Procedure

(S)-4-(3-(2,2,2-trifluoroethylamino)pyrrolidin-1-yl)-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (156 mg, 0.32 mmol) was dissolved in 1,4-dioxane (0.4 mL) and then treated with 48% HBr(aq) (0.4 mL) and heated at 60° C. for 20 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 yellow solid (5.0 mg, 5%). 1H NMR (400 MHz, d6-DMSO) δ 8.81 (s, 1H), 8.47 (s, 1H), 8.15 (d, J=5.8, 1H), 6.43 (d, J=5.8, 1H), 3.95 (m, 1H), 3.81 (m, 1H), 3.68 (m, 1H), 3.60-3.50 (m, 2H), 2.81 (m, 1H), 2.14 (m, 1H), 2.02-1.88 (m, 1H). LCMS (Method D): RT=7.71 min, M+H+=361.0.

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-85f6bc263de148398d28b2680080b312
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

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