Acetyl chloride → HCID 178474523, compound

HRID 2173991Notes

Reaction equation

HRID 2173991 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([CH2:13][C:14]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([C:23]#[N:24])=[CH:22][C:16]=3[N:15]=2)=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[CH:6]2.C([O-])(O)=O.[Na+].[C:30](Cl)(=[O:32])[CH3:31]>C(Cl)Cl>[C:23]([C:21]1[CH:20]=[CH:19][C:17]2[NH:18][C:14]([CH2:13][C:4]3[C:3]([CH2:2][NH:1][C:30](=[O:32])[CH3:31])=[CH:11][C:10]([CH3:12])=[C:9]4[C:5]=3[CH:6]=[CH:7][NH:8]4)=[N:15][C:16]=2[CH:22]=1)#[N:24]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 178426456HCID 178426456, compound

Product 1

HCID 178474523HCID 178474523, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-((5-(aminomethyl)-7-methyl-1H-indol-4-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile (20 mg, 0.063 mmol) in CH2Cl2 (1 mL)/5% aq. NaHCO3 (2 mL) was added acetyl chloride (45 μL, 0.634 mmol), and then the mixture was stirred at room temperature for 1 hr. The reaction was quenched by methylamine in EtOH (33%, 2 mL), and then stirred for 0.5 h. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organics were washed with H2O and brine, dried over Na2SO4, and filtered. After concentration the residue was purified by silica gel flash column chromatography (CH2Cl2/2M NH3 in MeOH=94/6) to give the title compound. 1H NMR (400 MHz, DMSO-d6 with about 5 μL TFA) δ ppm 11.16 (br. s., 1H), 8.47 (t, J=5.31 Hz, 1H), 8.10 (s, 1H), 7.69 (d, J=8.30 Hz, 1H), 7.65 (dd, J=1.00, 8.30 Hz, 1H), 7.30 (dd, J=2.80, 3.00 Hz, 1H), 6.91 (s, 1H), 6.49 (dd, J=1.80, 3.00 Hz, 1H), 4.64 (s, 2H), 4.42 (d, J=5.31 Hz, 2H), 2.45 (s, 3H), 1.79 (s, 3H). HRMS calcd. for C21H19N5O (M+H)+ 358.1662. found 358.1660.

Workup

  1. customThe reaction was quenched by methylamine in EtOH (33%, 2 mL)
  2. stirringstirred for 0.5 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2
  5. washThe combined organics were washed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationAfter concentration the residue
  9. customwas purified by silica gel flash column chromatography (CH2Cl2/2M NH3 in MeOH=94/6)

Sources & evidence

ORD record
ord-ba4eeb7beb2143e187a8aae2f4128b21
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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