1,1'-Carbonyldiimidazole → HCID 68670404, compound

HRID 2047397Notes

Reaction equation

HRID 2047397 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:26]([OH:28])=O)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[CH:32][C:31]=1[C:42]1[NH:46][C:45]2[CH:47]=[CH:48][CH:49]=[CH:50][C:44]=2[N:43]=1.CCN(C(C)C)C(C)C>C(#N)C>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH2:22][CH:23]([C:26]([N:39]2[CH2:40][CH2:41][N:36]([C:33]3[CH:34]=[CH:35][C:30]([F:29])=[C:31]([C:42]4[NH:43][C:44]5[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=5[N:46]=4)[CH:32]=3)[CH2:37][CH2:38]2)=[O:28])[CH2:24][CH2:25]1)=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 68670575HCID 68670575, compound

Product 1

HCID 68670404HCID 68670404, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

CDI (0.047 g, 0.29 mmol) was added to a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (0.07 g, 0.29 mmol) in acetonitrile (2.50 mL). The resulting solution was stirred at room temperature for 5 hours. 2-(2-Fluoro-5-piperazin-1-yl-phenyl)-1H-benzoimidazole (0.10 g, 0.27 mmol) and DIPEA (0.05 mL, 0.26 mmol) were added and reaction was heated at 65° C. overnight. Reaction was cooled to room temperature and solvent was removed under reduced pressure. DCM (2 mL) was added to the crude, organic solution was washed with water (2×4 mL) and with saturated Na2CO3 solution (2×4 mL) and concentrated. The crude reaction mixture was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to 100% AcOEt) to afford 0.08 g of the title compound (60%).

Workup

  1. customreaction
  2. temperaturewas heated at 65° C. overnight
  3. customReaction
  4. temperaturewas cooled to room temperature
  5. customsolvent was removed under reduced pressure
  6. additionDCM (2 mL) was added to the crude, organic solution
  7. washwas washed with water (2×4 mL) and with saturated Na2CO3 solution (2×4 mL)
  8. concentrationconcentrated
  9. customThe crude reaction mixture
  10. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to 100% AcOEt)

Sources & evidence

ORD record
ord-ca7289c82d484f56b401d7d5aa1aa59a
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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