Hydrogen Bromide → HCID 58266682, compound

HRID 1505960Notes

Reaction equation

[C:1]([C:3]1[N:11]=[CH:10][C:9]2[N:8](COCC[Si](C)(C)C)[C:7]3[N:20]=[CH:21][CH:22]=[C:23]([NH:24][CH:25]4[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]4)[C:6]=3[C:5]=2[CH:4]=1)#[N:2].Br.[OH-].[Na+].Cl>O1CCOCC1>[NH:28]1[CH2:27][CH2:26][CH:25]([NH:24][C:23]2[C:6]3[C:5]4[CH:4]=[C:3]([C:1]#[N:2])[N:11]=[CH:10][C:9]=4[NH:8][C:7]=3[N:20]=[CH:21][CH:22]=2)[CH2:30][CH2:29]1

Participants

Conditions

Temperature: 75 °C

Procedure

tert-Butyl 4-{6-cyano-9-(2-trimethylsilanylethoxymethyl)-dipyrido[2,3-b;4′,3′-d]pyrrol-4-ylamino}piperdine-1-carboxylate (80 mg, 0.14 mmol) was dissolved in 1,4-dioxane (0.4 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% formic acid) over 30 min, 35 mL/min) to afford the title compound as a pale yellow solid (20 mg, 30% over two steps). 1H NMR (DMSO-D6, 400 MHz): 9.08 (s, 1H), 8.83 (s, 1H), 8.20 (d, J=5.9 Hz, 1H), 6.63 (d, J=6.0 Hz, 1H), 6.46 (d, J=8.0 Hz, 1H), 3.74 (m, 1H), 3.11 (m, 2H), 2.71 (m, 2H), 1.97 (m, 2H), 1.70 (m, 2H). LCMS (Method E): RT=2.28 min, M+H+=293.

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% formic acid) over 30 min, 35 mL/min)

Sources & evidence

ORD record: ord-0773861ac6b148fd981d5f691e48a0d0
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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