1,1'-Carbonyldiimidazole → HCID 10073367, compound

HRID 1178647Notes

Reaction equation

HRID 1178647 reaction equation
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[C:13]([C:15]1[C:16]([NH:33][C:34]2[CH:39]=[C:38]([O:40][CH3:41])[C:37]([Cl:42])=[CH:36][C:35]=2[Cl:43])=[C:17]2[S:23][C:22]([C:24]3[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][CH:25]=3)=[CH:21][C:18]2=[N:19][CH:20]=1)#[N:14]>CN(C)C=O>[C:13]([C:15]1[C:16]([NH:33][C:34]2[CH:39]=[C:38]([O:40][CH3:41])[C:37]([Cl:42])=[CH:36][C:35]=2[Cl:43])=[C:17]2[S:23][C:22]([C:24]3[CH:32]=[CH:31][C:27]([C:28]([NH2:3])=[O:30])=[CH:26][CH:25]=3)=[CH:21][C:18]2=[N:19][CH:20]=1)#[N:14]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 11754454HCID 11754454, compound

Product 1

HCID 10073367HCID 10073367, compoundYield 9.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

1,1′-Carbonyldiimidazole (100 mg, 0.61 mmol) is added to a suspension of 4-{6-cyano-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-2-yl]benzoic acid (130 mg, 0.28 mmol) in 10 mL of N,N-dimethylformamide. After stirring at 60° C. for 2 hours the reaction mixture is allowed to cool to room temperature and ammonia gas is bubbled through the mixture for 15 minutes. The mixture is stirred at room temperature for an additional 60 minutes and poured into 50 g of ice and stirred for 30 minutes. The mixture is adjusted to pH 4 with concentrated hydrochloric acid and stirred for 60 minutes. The resulting precipitate is collected by filtration washing with water and dried under reduced pressure. The resulting solid is purified by flash column chromatography eluting with a gradient of ethyl acetate to 20% methanol in ethyl acetate to provide 12.3 mg of 4-{6-cyano-7-[(2,4-dichloro-5-methoxyphenyl)amino]thieno[3,2-b]pyridine-2-yl}benzamide as a gray solid, mp>300° C.; 1H NMR (DMSO-d6) δ3.86 (s, 3H), 7.40 (s, 1H), 7.48 (s, 1H), 7.78 (s, 1H), 7.82 (d, J=8 Hz, 2H), 7.97 (d, J=8 Hz, 2H), 8.06 (s, 2H), 8.08 (s, 1H), 8.63 (s, 1H), 9.78 (s, 1H); MS 468.9, 471.1 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. customammonia gas is bubbled through the mixture for 15 minutes
  3. stirringThe mixture is stirred at room temperature for an additional 60 minutes
  4. additionpoured into 50 g of ice
  5. stirringstirred for 30 minutes
  6. stirringstirred for 60 minutes
  7. filtrationThe resulting precipitate is collected by filtration
  8. washwashing with water
  9. customdried under reduced pressure
  10. customThe resulting solid is purified by flash column chromatography
  11. washeluting with a gradient of ethyl acetate to 20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-03c5733bc6a940a2b6d96fc1544b3d54
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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