1,1'-Carbonyldiimidazole → HCID 178514087, compound

HRID 1639621Notes

Reaction equation

HRID 1639621 reaction equation
[N:1]1([CH2:7][C:8]2[CH:22]=[CH:21][C:11]3[NH:12][C:13]([C:15]4[C:19]([NH2:20])=[CH:18][NH:17][N:16]=4)=[N:14][C:10]=3[CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1N=CN([C:28]([N:30]2C=NC=C2)=[O:29])C=1.[F:35][C:36]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:37]=1[CH2:38]N>C1COCC1>[F:35][C:36]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:37]=1[CH2:38][N:20]([C:19]1[C:15]([C:13]2[NH:12][C:11]3[CH:21]=[CH:22][C:8]([CH2:7][N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:9][C:10]=3[N:14]=2)=[N:16][NH:17][CH:18]=1)[C:28]([NH2:30])=[O:29]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 1235632,6-DifluorobenzylamineHCID 178508054HCID 178508054, compound

Product 1

HCID 178514087HCID 178514087, compoundYield 19.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-ylamine (Example 1E.), (100 mg, 0.33 mmol), and CDI (217 mg, 1.34 mmol) in THF (2 ml) was subjected to microwave irradiation (150° C., 150 W) for 15 minutes. 2,6-Difluoro-benzylamine (384 mg, 2.68 mmol) was then added and the reaction mixture irradiated again under identical conditions for a further 15 minutes. After cooling, the heterogeneous mixture was filtered, the filtrate was concentrated and the residue purified by column chromatography (SiO2 eluting with gradient-DCM:MeOH:AcOH:H2O (240:20:3:2) (DMAW240 to (120:18:3:2) (DMAW120) to give 1-(2,6-difluoro-benzyl)-[3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-urea (30 mg 19%). (LC/MS Acidic: Rt 1.84 [M+H]+ 468).

Workup

  1. customwas subjected to microwave irradiation (150° C., 150 W) for 15 minutes
  2. customthe reaction mixture irradiated again under identical conditions for a further 15 minutes
  3. temperatureAfter cooling
  4. filtrationthe heterogeneous mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. customthe residue purified by column chromatography (SiO2 eluting with gradient-DCM:MeOH:AcOH:H2O (240:20:3:2) (DMAW240 to (120:18:3:2) (DMAW120)

Sources & evidence

ORD record
ord-b5252224398c4fc49215fedad04782bf
Source dataset
uspto-grants-2012_02
Patent number
US08110573B2

Reaction notes

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