Phosphorus tribromide → US9433622, Dmx-156

HRID 55899Notes

Reaction equation

HRID 55899 reaction equation
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([C:28]#[N:29])=[N:9][C:10]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]4[CH:21]=[N:22][C:23]([CH2:26]O)=[CH:24][CH:25]=4)[N:14]=3)=[CH:11][CH:12]=2)[CH2:3]1.P(Br)(Br)Br.[O:34]=[C:35]1[CH2:40][NH:39][CH2:38][CH2:37][NH:36]1>CC#N>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]([C:28]#[N:29])=[N:9][C:10]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]4[CH:21]=[N:22][C:23]([CH2:26][N:39]5[CH2:38][CH2:37][NH:36][C:35](=[O:34])[CH2:40]5)=[CH:24][CH:25]=4)[N:14]=3)=[CH:11][CH:12]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 24614Phosphorus tribromideHCID 231360Piperazin-2-oneHCID 903695443-((S)-3-Fluoro-pyrrolidin-1-yl)-6-[2-(6-hydroxymethyl-pyridin-3-ylamino)-pyrimidin-4-yl]-pyridine-2-carbonitrile

Product 1

HCID 90356780US9433622, Dmx-156Yield 6.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound 82 (40 mg, 0.10 mmol) was dissolved in MeCN (5 mL). Phosphorous tribromide (50 μL, 0.53 mmol) was added and the reaction mixture was heated under reflux for 0.5 hours. The reaction was cooled to rt and 2-oxopiperazine (100 mg, 0.99 mmol) was added and the reaction mixture stirred at rt for 16 hours. The solvent was removed in vacuo and the residue purified by reverse phase preparative LC-MS. Fractions contained the desired product were combined and the MeOH removed in vacuo. The resulting aqueous solution was frozen (−78° C.) and the solvent evaporated in vacuo (freeze dried). The title compound (3 mg, 6%) was obtained as an off-white solid. LCMS, Rt=6.15 min (MeOH-FA method), m/z 474 (MH+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 0.5 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue purified by reverse phase preparative LC-MS
  5. customthe MeOH removed in vacuo
  6. temperatureThe resulting aqueous solution was frozen (−78° C.)
  7. customthe solvent evaporated in vacuo (freeze dried)

Sources & evidence

ORD record
ord-56f9dfa100104078a8c79c39ac5578f0
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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