2-Bromopyridine → HCID 178479691, compound

HRID 658114Notes

Reaction equation

HRID 658114 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[NH:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[NH:15][C:14]1=[C:22]([C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1)=[O:34])[C:23]([C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=[O:29])=[O:24].[Cl-:42].[NH4+]>C1COCC1>[ClH:42].[NH:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[NH:15][C:14]1=[C:22]([C:23]([C:25]1[CH:32]=[CH:31][CH:30]=[C:27]([CH:28]([OH:29])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:26]=1)=[O:24])[C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1)=[O:34]

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 25517Ammonium ChlorideHCID 178418339ButyllithiumHCID 178519574HCID 178519574, compound

Product 1

HCID 178479691HCID 178479691, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 0.33 ml portion of 2-bromopyridine was dissolved in 3 ml of THF, and the solution was cooled to −78° C., mixed with 2.2 ml of n-butyl lithium and then stirred at the same temperature for 30 minutes. This solution was poured at −78° C. into a solution prepared by dissolving 3-[2-(1,3-dihydro-2H-benzimidazol-2-ylidene)-3-(3-fluorophenyl)-3-oxopropanoyl]benzaldehyde in 10 ml of THF. This was slowly risen to room temperature and mixed with 50 ml of saturated ammonium chloride aqueous solution. This was extracted with ethyl acetate, dried with sodium sulfate and then concentrated, and the thus formed residue was purified by a silica gel column chromatography (chloroform:methanol from 100:0 to 90:10). By subjecting the thus obtained reddish brown solid to salt formation with 4N HCl/EtOAC (0.2 ml), 151 mg (42%) of 2-(1,3-dihydro-2H-benzimidazol-2-ylidene)-1-(3-fluorophenyl)-3-{3-[hydroxy(pyridin-2-yl)methyl]phenyl}propane-1,3-dione hydrochloride (Example 11-1) was obtained. FA: 466

Workup

  1. additionThis solution was poured at −78° C. into a solution
  2. customprepared
  3. customThis was slowly risen to room temperature
  4. extractionThis was extracted with ethyl acetate
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customthe thus formed residue was purified by a silica gel column chromatography (chloroform:methanol from 100:0 to 90:10)

Sources & evidence

ORD record
ord-9b01660c338a4d9484446a002dd20b07
Source dataset
uspto-grants-2011_12
Patent number
US08076367B2

Reaction notes

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