Toluene → N-((5-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-3-yl)methyl)ethanesulfonamide

HRID 1897794Notes

Reaction equation

HRID 1897794 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[C:14]([CH:17]=3)[CH:15]=O)[N:7]([CH3:18])[C:6]=2[CH:19]=1.[CH2:20]([S:22]([NH2:25])(=[O:24])=[O:23])[CH3:21].C1(C)C=CC=CC=1.[BH4-].[Na+]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[CH:17]=[C:14]([CH2:15][NH:25][S:22]([CH2:20][CH3:21])(=[O:24])=[O:23])[CH:13]=[N:12][CH:11]=3)[N:7]([CH3:18])[C:6]=2[CH:19]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 73702EthanesulfonamideHCID 4311764Sodium borohydrideHCID 595784235-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)nicotinaldehyde

Product 1

HCID 49820746N-((5-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-3-yl)methyl)ethanesulfonamide

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A flask was charged with 5-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)nicotinaldehyde (100 mg, 0.368 mmol), ethanesulfonamide (80 mg, 0.736 mmol) and toluene (3 mL), and titanium isopropoxide (157 mg, 0.552 mmol) was added dropwise. The mixture was stirred at 120° C. overnight. The mixture was concentrated in vacuo and the residue was taken up in DCM (20 mL) and MeOH (20 mL), and NaBH4 (0.0557 g, 1.47 mmol) was added at 0° C. The mixture was stirred at 0° C. for 30 min. Water (1 mL) was added and the mixture was stirred for 5 min. DMF (5 mL) was added and the suspension was filtered. The filtrate was purified by Xbridge RP 18 eluting with a 20 to 70% ACN-water gradient to give the title compound. HRMS: (ESI) m/z 365.0839 [(M+H)+ Calcd for C16H18ClN4O2S 365.0834]. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 (t, J=7.33 Hz, 3H) 3.06 (q, J=7.33 Hz, 2H) 3.92 (s, 3H) 4.33 (s, 2H) 7.30 (dd, J=8.46, 2.15 Hz, 1H) 7.73 (d, J=8.59 Hz, 1H) 7.77 (s, 1H) 7.86 (d, J=2.02 Hz, 1H) 8.25 (t, J=2.02 Hz, 1H) 8.72 (d, J=2.02 Hz, 1H) 8.97 (d, J=2.27 Hz, 1H).

Workup

  1. additionwas added dropwise
  2. concentrationThe mixture was concentrated in vacuo
  3. stirringThe mixture was stirred at 0° C. for 30 min
  4. stirringthe mixture was stirred for 5 min
  5. filtrationthe suspension was filtered
  6. customThe filtrate was purified by Xbridge RP 18 eluting with a 20 to 70% ACN-water gradient

Sources & evidence

ORD record
ord-4f7a05dfb5624757b99b87e9eb39aae0
Source dataset
uspto-grants-2013_08
Patent number
US08519142B2

Reaction notes

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