Thionyl Chloride → HCID 11466081, compound

HRID 2374908Notes

Reaction equation

HRID 2374908 reaction equation
[C:1]([C:9]1[CH:10]=[C:11]([CH:36]=[CH:37][CH:38]=1)[C:12]([NH:14][CH:15]([C:17]1[N:22]=[N:21][C:20]([NH:23][C:24]2[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26]([O:34][CH3:35])[CH:25]=2)=[N:19][CH:18]=1)[CH3:16])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O>ClCCCl.CN(C)C=O>[CH3:16][C:15]1[N:14]=[C:12]([C:11]2[CH:10]=[C:9]([C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:8])[CH:38]=[CH:37][CH:36]=2)[N:22]2[C:17]=1[CH:18]=[N:19][C:20]([NH:23][C:24]1[CH:25]=[C:26]([O:34][CH3:35])[C:27]([O:32][CH3:33])=[C:28]([O:30][CH3:31])[CH:29]=1)=[N:21]2

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 58711926HCID 58711926, compound2×

Product 1

HCID 11466081HCID 11466081, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-benzoyl-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (Intermediate 28) (95 mg, 0.18 mmol) in 1,2-dichloroethane was added catalytic dimethylformamide (3 drops) and thionyl chloride (0.36 mL, 5.0 mmol). The mixture was heated at 50° C. for 14 hours. After cooling to room temperature the mixture was concentrated under vacuum. The resulting solid was taken up in a mixture of dichloromethane and methanol, then concentrated ammonium hydroxide was added until the solution was basic. The solution was then concentrated under vacuum and purified by reverse-phase HPLC to give (3-{5-methyl-2-[(3,4,5-trimethoxyphenyl)-amino]imidazo[5,1-f][1,2,4]triazin-7-yl}phenyl)(phenyl)-methanone (8 mg) as a yellow solid. 1H NMR (DMSO-d6): δ9.63 (s, 1H), 9.26 (s, 1H), 8.80 (d, J=7.87 Hz, 1H), 8.61 (s, 1H), 7.74-7.80 (m, 3H), 7.63 (t, J=7.69 Hz, 2H), 7.68 (t, J=7.69 Hz, 2H), 7.05 (s, 2H), 3.68 (s, 6H), 3.62 (s, 3H), 2.52 (s, 3H). MS m/z 495 (M+1).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated under vacuum
  3. additionThe resulting solid was taken up in a mixture of dichloromethane and methanol
  4. additionconcentrated ammonium hydroxide was added until the solution
  5. concentrationThe solution was then concentrated under vacuum
  6. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-184db0ad8abb493bb35cb1440d4d05cf
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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