Toluene → HCID 10115737, compound

HRID 583748Notes

Reaction equation

HRID 583748 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[S:27])[C:12]3[CH:19]=[C:18]([CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[S:9])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C[O:41]C1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1.C1(C)C=CC=CC=1>ClC(Cl)C.ClCCl>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[S:27])[C:12]3[CH:19]=[C:18]([CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:41])=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[S:27])[C:12]3[CH:19]=[C:18]([CH2:20][N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[S:9])=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 87949Lawesson's reagentHCID 3251421Potassium bis(trimethylsilyl)amideHCID 10115737HCID 10115737, compound

Product 2

HCID 10115737HCID 10115737, compoundHCID 10225704HCID 10225704, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Preparation of N-(4-Chlorobenzyl)-7-methyl-2-(4-morpholinylmethyl)-4-thioxo-4,7-dihydrothieno[2,3-b]pyridine-5-carbothioamide, (A-2 of Chart A) A-1 (570 mg, 1.32 mmol) was dissolved in dichloroethane (80 mL) followed by the addition of KHMDS (0.5 M, 2.64 mL, 1.32 mmol, 1 equiv.). Then Lawesson's reagent (1.1 g, 2.64 mmol, 2.0 equiv.) and toluene (80 mL) was added and the resulting mixture was heated at reflux for 6 h. The reaction was cooled to rt, diluted with dichloromethane, washed with water, Na2CO3, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (heptane/EtOAc 1/1, ¼, 0/1 then DCM/MeOH 19/1) to afford 248 mg of crude N-(4-chlorobenzyl)-7-methyl-2-(4-morpholinylmethyl)-4-thioxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboamide and 139 mg of crude N-(4-chlorobenzyl)-7-methyl-2-(4-morpholinylmethyl)-4-thioxo-4,7-dihydrothieno[2,3-b]pyridine-5-carbothioamide A-2. The crude A-2 was purified by multiple silica gel chromatography (heptane/EtOAc 1/1, ¼, 0/1 then DCM/MeOH 1/0, 50/1, 19/1) to afford 55 mg (9%) of pure tan solid.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 6 h
  3. washwashed with water, Na2CO3, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (heptane/EtOAc 1/1, ¼, 0/1

Sources & evidence

ORD record
ord-1ba51d34b66b41238914ffbfa3406bf8
Source dataset
uspto-grants-2005_08
Patent number
US06924283B2

Reaction notes

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