Dimethylformamide → HCID 178432050, compound

HRID 44534Notes

Reaction equation

HRID 44534 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[Cl-].[NH4+].CN(C)C=O.[CH3:12][C:13]1[N:17]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:16]2[CH:29]=[C:30]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:31]=[C:32]([C:33]#[N:34])[C:15]=2[N:14]=1>O>[CH3:12][C:13]1[N:17]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:16]2[CH:29]=[C:30]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:31]=[C:32]([C:33]3[NH:34][N:3]=[N:2][N:1]=3)[C:15]=2[N:14]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 569596832-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrile

Product 1

HCID 178432050HCID 178432050, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a two 5 mL MW vial was added in 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrile, prepared as described in Example 24 (80 mg, 0.209 mmol), sodium azide (109 mg, 1.673 mmol) and ammonium chloride (90 mg, 1.673 mmol) and N,N-Dimethylformamide (DMF) (2 mL). The reaction mixture was subjected to MW irradiation for 15 min at 180° C., then 80 min at 185° C. LC-MS analysis only showed 30% conversion; however, heating for longer time caused the decomposition of the product. The two reaction mixtures were combined. The combined mixture was added in water (10 mL) and extracted with DCM (30 mL×4). The combined organic phases were washed with saturated NH4Cl solution, dried, and concentrated. The reaction was subjected to purification on a silica column (20˜60% EtOAc/Hexane) and then (1˜5% MeOH/DCM) to give the product (24 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.53 (s, 3H) 3.08-3.15 (m, 4H) 3.68-3.75 (m, 4H) 6.10 (s, 2H) 6.40 (d, J=7.33 Hz, 1H) 7.26-7.39 (m, 2H) 7.56-7.74 (m, 3H) 7.88 (d, J=8.34 Hz, 1H) 8.03 (d, J=8.08 Hz, 1H) 8.26 (d, 1H). MS (ES+) m/e 426.0 [M+H]+.

Workup

  1. customprepared
  2. customThe reaction mixture was subjected to MW irradiation for 15 min at 180° C.
  3. custom80 min
  4. customat 185° C
  5. temperaturehowever, heating for longer time
  6. customThe two reaction mixtures
  7. extractionextracted with DCM (30 mL×4)
  8. washThe combined organic phases were washed with saturated NH4Cl solution
  9. customdried
  10. concentrationconcentrated
  11. customThe reaction was subjected to purification on a silica column (20˜60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-1ab8b1b57d2741b6a298c30c933b7263
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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