Triethylamine → N-cyclopropyl-3-[2-(2,4-difluorophenoxy)-6-oxo-6H-pyrido[1,2-b]pyridazin-5-yl]-4-methoxybenzamide

HRID 1454960Notes

Reaction equation

HRID 1454960 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:11]=[CH:12][C:13](=[O:26])[C:14]=2[C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=2[O:24][CH3:25])[C:18]([OH:20])=O)[N:10]=1.C(N(CC)CC)C.C(OC(Cl)=O)C.[CH:45]1([NH2:48])[CH2:47][CH2:46]1>C(Cl)Cl>[CH:45]1([NH:48][C:18](=[O:20])[C:17]2[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:15]([C:14]3[C:13](=[O:26])[CH:12]=[CH:11][N:9]4[C:8]=3[CH:7]=[CH:6][C:5]([O:4][C:3]3[CH:27]=[CH:28][C:29]([F:31])=[CH:30][C:2]=3[F:1])=[N:10]4)[CH:16]=2)[CH2:47][CH2:46]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 69828CyclopropylamineHCID 575312343-(2-(2,4-Difluorophenoxy)-6-oxo-6H-pyrido[1,2-b]pyridazin-5-yl)-4-methoxybenzoic acid

Product 1

HCID 16749900N-cyclopropyl-3-[2-(2,4-difluorophenoxy)-6-oxo-6H-pyrido[1,2-b]pyridazin-5-yl]-4-methoxybenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of Intermediate 1 in CH2Cl2 was added triethyl amine and ethylchloroformate at 0° C. The mixture was warmed to ambient temperature and stirred for 10 min. The reaction was complete by LCMS analysis and concentrated in vacuo to yield crude residue. To the crude residue was added CH2Cl2 and cyclopropyl amine, followed by stirring for ½ hr. LCMS indicated the reaction was complete. The reaction was diluted with CH2Cl2, washed with 0.5 N NaOH, H2O, brine, dried over MgSO4, and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc/CH2Cl2/MeOH).

Workup

  1. concentrationconcentrated in vacuo
  2. customto yield crude residue
  3. stirringby stirring for ½ hr
  4. washwashed with 0.5 N NaOH, H2O, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified via silica gel chromatography (EtOAc/CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-1a7c0f80ffb245ffa7ee7dbc5d71ecd7
Source dataset
uspto-grants-2009_01
Patent number
US07482345B2

Reaction notes

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