Phosphorus oxychloride → 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrile

HRID 2174782Notes

Reaction equation

HRID 2174782 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=[C:21]([C:22]([NH2:24])=O)[C:4]=2[N:3]=1.O=P(Cl)(Cl)Cl>ClCCl.CN(C=O)C>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=[C:21]([C:22]#[N:24])[C:4]=2[N:3]=1

Participants

5

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 569598302-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamide

Product 1

HCID 569596832-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carbonitrileYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To the mixture of 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamide, prepared as described in Example 33 (0.4 g, 0.999 mmol) in Dichloromethane (DCM) (50 mL) was added in POCl3 (0.931 mL, 9.99 mmol) and followed by the addition of ten drops of DMF. The reaction was stirred at rt for 1 h. The mixture was quenched with aqueous sodium bicarbonate solution. The aqueous phase was extracted with DCM (100 mL). The combined organic phase was washed with Brine then dried (MgSO4), filtered and the solvent removed in-vacuo. The crude was purified on silica (20˜50% EtOAc/Hexane) to give the product (0.246 g, 64%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.45 (s, 3H), 2.96-3.15 (m, 4H), 3.62-3.72 (m, 4H), 6.05 (s, 2H), 6.32 (d, J=7.07 Hz, 1H), 7.29-7.44 (m, 3H), 7.57-7.74 (m, 2H), 7.86 (d, J=8.08 Hz, 1H), 8.02 (d, J=7.83 Hz, 1H) 8.22 (d, 1H), MS (ES+) m/z 383.2 [M+H]+.

Workup

  1. customprepared
  2. customThe mixture was quenched with aqueous sodium bicarbonate solution
  3. extractionThe aqueous phase was extracted with DCM (100 mL)
  4. washThe combined organic phase was washed with Brine
  5. dry with materialthen dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in-vacuo
  8. customThe crude was purified on silica (20˜50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-107b9f7266954e0a9cc86edc0a08b53a
Source dataset
uspto-grants-2015_06
Patent number
US09062003B2

Reaction notes

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