3-Cyano-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-6-carboxylic acid methoxy-methyl-amide → 5-Methyl-4-(4-phenoxy-phenylamino)-6-propynoyl-pyrrolo[1,2-b]pyridazine-3-carbonitrile

HRID 1796658Notes

Reaction equation

HRID 1796658 reaction equation
CON(C)[C:4]([C:6]1[C:7]([CH3:31])=[C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)=[C:12]([C:28]#[N:29])[CH:11]=[N:10][N:9]2[CH:30]=1)=[O:5].[C:33]([Mg]Br)#[CH:34]>C1COCC1.CCOCC>[CH3:31][C:7]1[C:6]([C:4](=[O:5])[C:33]#[CH:34])=[CH:30][N:9]2[C:8]=1[C:13]([NH:14][C:15]1[CH:16]=[CH:17][C:18]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:19][CH:20]=1)=[C:12]([C:28]#[N:29])[CH:11]=[N:10]2

Participants

5

Reactant 2

HCID 210250653-Cyano-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-6-carboxylic acid methoxy-methyl-amideHCID 178418486HCID 178418486, compound

Product 1

HCID 221797095-Methyl-4-(4-phenoxy-phenylamino)-6-propynoyl-pyrrolo[1,2-b]pyridazine-3-carbonitrileYield 54.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of amide from Example 417 (60 mg, 0.14 mmol) in THF (2 ml) at 0° C. was added ethynylmagnesium bromide (0.5 M in THF, 1.4 ml, 0.7 mmol). The reaction mixture was warmed to rt for 2 h, then heated at 50° C. for 2 h, and at rt overnight. Diluted with ether, washed with saturated NaHCO3, dried with Na2SO4. Concentrated in vacuo and purified by prep. TLC to give the title compound (30 mg, 32%) (5% MeOH—CHCl3). It has a retention time of 6.82 min (standard LCl method, 8 min run). LCMS Found: (M+H)+=393.2

Workup

  1. temperatureheated at 50° C. for 2 h
  2. customat rt
  3. customovernight
  4. washwashed with saturated NaHCO3
  5. dry with materialdried with Na2SO4
  6. concentrationConcentrated in vacuo
  7. custompurified by prep

Sources & evidence

ORD record
ord-641a13125ac043b99db598ecbaa818bf
Source dataset
uspto-grants-2006_04
Patent number
US07030112B2

Reaction notes

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