Dimethylformamide → 3-Cyano-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-7-carboxylic acid ethyl ester

HRID 1796647Notes

Reaction equation

HRID 1796647 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:10]2[N:11]=[CH:12][C:13]([C:16]#[N:17])=[C:14](O)[C:9]2=[CH:8][CH:7]=1)=[O:5])[CH3:2].CN(C=O)C.C([O-])([O-])=O.[K+].[K+].[O:29]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O=P(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:10]2[N:11]=[CH:12][C:13]([C:16]#[N:17])=[C:14]([NH:42][C:39]3[CH:38]=[CH:37][C:36]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:41][CH:40]=3)[C:9]2=[CH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8764(4-Aminophenoxy)benzeneHCID 11430Potassium CarbonateHCID 178468663HCID 178468663, compound

Product 1

HCID 210250973-Cyano-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-7-carboxylic acid ethyl esterYield 77.5%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

Compound 406E (110 mg, 0.476 mmol) was heated in POCl3 (1 ml) at 83-100° C. for 2 h. Excess POCl3 was removed on a rotary evaporator, and the residue was stripped with CH2Cl2 (2 ml). To the solid residue was added DMF (5 ml), K2CO3 (690 mg, 5 mmol) and 4-phenoxy-phenylamine (353 mg, 1.91 mmol) at 0° C. The reaction mixture was degassed and stirred at rt overnight. Solid was filtered off and the filtrate was concentrated, the residue was purified by silica gel flash column chromatography to give the 406 (147 mg, 78%) as a yellow solid (25% EtOAc—Hexanes). LCMS Found: (M+H)+=398.6

Workup

  1. customExcess POCl3 was removed on a rotary evaporator
  2. customThe reaction mixture was degassed
  3. filtrationSolid was filtered off
  4. concentrationthe filtrate was concentrated
  5. customthe residue was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-d7cca1229a09466996b970b8816400fb
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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