Benzyl Bromide → 4-((1-(6-Benzyl-3-chloro-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)-3-fluorobenzonitrile

HRID 713217Notes

Reaction equation

HRID 713217 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[N:9][CH:10]=[CH:11][C:5]2=[N:4][C:3]=1[N:12]1[CH2:17][CH2:16][CH:15]([O:18][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=2[F:27])[CH2:14][CH2:13]1.[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C>[CH2:28]([N:9]1[CH2:10][CH2:11][C:5]2[C:6](=[N:7][C:2]([Cl:1])=[C:3]([N:12]3[CH2:13][CH2:14][CH:15]([O:18][C:19]4[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=4[F:27])[CH2:16][CH2:17]3)[N:4]=2)[CH2:8]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 5049666Sodium triacetoxyborohydrideHCID 1181591914-((1-(3-Chloropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)-3-fluorobenzonitrile

Product 1

HCID 1181593824-((1-(6-Benzyl-3-chloro-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)-3-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Benzyl bromide was purified by filtration through a plug of basic alumina prior to use. A solution of 4-((1-(3-chloropyrido[3,4-b]pyrazin-2-yl)piperidin-4-yl)oxy)-3-fluorobenzonitrile (200 mg, 0.521 mmol) and benzyl bromide (0.062 mL, 0.521 mmol) in ACN (2.60 mL) was heated at 80° C. for 3 h. The reaction mixture was allowed to cool to room temperature and sodium triacetoxyborohydride (331 mg, 1.563 mmol) was added. After stirring for 1 h at room temperature, the reaction mixture was quenched with saturated aqueous NaCl (1 mL). After bubbling ceased, the reaction mixture was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 35% to 70% ACN gradient to give the title compound, as a TFA salt, as a yellow oil (117.9 mg, 38.2%). ESI-MS m/z [M+H]+ 478.5.

Workup

  1. filtrationBenzyl bromide was purified by filtration through a plug of basic alumina
  2. customthe reaction mixture was quenched with saturated aqueous NaCl (1 mL)
  3. customAfter bubbling
  4. customthe reaction mixture was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column

Sources & evidence

ORD record
ord-8de4c3e9ddf4422d81ed9af2c1fe1123
Source dataset
uspto-grants-2015_11
Patent number
US09181249B2

Reaction notes

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