Ethyl Acetate → Tert-butyl (r)-1-(6-(3-chlorophenylamino)pyridazin-3-ylaminocarbamoyl)ethylcarbamate

HRID 446899Notes

Reaction equation

HRID 446899 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:10]=[N:11][C:12]([NH:15][NH2:16])=[CH:13][CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[NH:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:18]([C:20](O)=[O:21])[CH3:19].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OCC)(=O)C>CN(C=O)C.CCN(C(C)C)C(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:10]=[N:11][C:12]([NH:15][NH:16][C:20]([C@H:18]([NH:17][C:23](=[O:24])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH3:19])=[O:21])=[CH:13][CH:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 637606BOC-D-alanineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59363292N-(3-chlorophenyl)-6-hydrazinylpyridazin-3-amine

Product 1

HCID 59363297Tert-butyl (r)-1-(6-(3-chlorophenylamino)pyridazin-3-ylaminocarbamoyl)ethylcarbamateYield 34%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

(Step 1-iii) N-(3-chlorophenyl)-6-hydrazinylpyridazin-3-amine (2.4 g, 10 mmol) was combined with Boc-D-Ala-OH (2.0 g, 10.5 mmol), HBTU (4.4 g, 11.6 mmol) in DMF and DIEA (2.0 mL (11.5 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours and poured into ethyl acetate/saturated sodium bicarbonate. The organic layer was dried over sodium sulfate, concentrated to an oil, and purified by silica gel column chromatography (EtOAc to 10% MeOH/EtOAc), to give the product, tert-butyl (R)-1-(6-(3-chlorophenylamino)pyridazin-3-ylaminocarbamoyl)ethylcarbamate (1.38 g, 3.4 mmol, 34%).

Workup

  1. additionwas added
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated to an oil
  4. custompurified by silica gel column chromatography (EtOAc to 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-fb5fc266444147fa98fa219eeefa7766
Source dataset
uspto-grants-2013_07
Patent number
US08481538B2

Reaction notes

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