Thionyl Chloride → N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-[(6-methyl-3-pyridyl)carbonyl]thiourea

HRID 721929Notes

Reaction equation

HRID 721929 reaction equation
S(Cl)(Cl)=O.CC1C=CC(C(O)=O)=CN=1.CC1N=CC(C(Cl)=O)=CC=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][C:36]=1[O:37][CH3:38])[N:33]=[CH:32][N:31]=[C:30]2[O:39][C:40]1[CH:46]=[CH:45][C:43]([NH2:44])=[CH:42][CH:41]=1.[CH3:47][C:48]1[N:53]=[CH:52][C:51]([C:54]([N:56]=[C:57]=[S:58])=[O:55])=[CH:50][CH:49]=1>C1(C)C=CC=CC=1.C(O)C>[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][C:36]=1[O:37][CH3:38])[N:33]=[CH:32][N:31]=[C:30]2[O:39][C:40]1[CH:46]=[CH:45][C:43]([NH:44][C:57]([NH:56][C:54]([C:51]2[CH:52]=[N:53][C:48]([CH3:47])=[CH:49][CH:50]=2)=[O:55])=[S:58])=[CH:42][CH:41]=1

Participants

8

Reactant 5

HCID 24386Thionyl ChlorideHCID 1378606-Methylnicotinic acidHCID 116163634-(6,7-Dimethoxyquinazolin-4-yloxy)anilineHCID 218904586-Methylnicotinoyl chlorideHCID 218912096-Methyl-3-pyridinecarbonyl isothiocyanate

Product 1

HCID 21890664N-{4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-[(6-methyl-3-pyridyl)carbonyl]thioureaYield 89%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

Toluene (20 ml) and thionyl chloride (1 ml) were added to commercially available 6-methylnicotinic acid (80 mg), and the mixture was heated at 100° C. for one hr. The solvent was removed by distillation, and 6-methyl-3-pyridinecarbonyl isothiocyanate was prepared using the resultant 6-methyl-3-pyridinecarbonyl chloride as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 6-methyl-3-pyridinecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (71 mg, yield 89%).

Workup

  1. customThe solvent was removed by distillation, and 6-methyl-3-pyridinecarbonyl isothiocyanate
  2. customwas prepared
  3. concentrationThe reaction solution was concentrated
  4. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-321c448b3b504191a34b2ef7a45faa1c
Source dataset
uspto-grants-2006_11
Patent number
US07135466B2

Reaction notes

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