1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-(benzyloxy)-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide

HRID 1661106Notes

Reaction equation

HRID 1661106 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([NH:14][NH2:15])=[N:12][N:11]([CH2:16][C:17]3[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:10](=[O:28])[C:9]=2[C:29]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.[CH2:37]([O:44][C@H:45]([CH3:49])[C:46](O)=[O:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CCOC(C)=O.C1COCC1>[CH2:37]([O:44][C@H:45]([CH3:49])[C:46]([NH:15][NH:14][C:13]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:9]([C:29]2[CH:30]=[CH:31][C:32]([C:33]#[N:34])=[CH:35][CH:36]=2)[C:10](=[O:28])[N:11]([CH2:16][C:17]2[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=2)[N:12]=1)=[O:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7000104(2R)-2-phenylmethoxypropanoic acidHCID 671287294-(5-(4-Chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

Product 1

HCID 67128707(R)-2-(benzyloxy)-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazideYield 76.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask was added 4-(5-(4-chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile (70 mg, 0.1367 mmol), prepared as described in Example 2B, (R)-2-(benzyloxy)propanoic acid (25 mg, 0.1367 mmol), EDAC (30 mg, 0.150 mmol), HOBT (20.3 mg, 0.150 mmol), THF (5 ml) and diisopropylethyl amine (19.4 mg, 0.150 mmol). The reaction was stirred at rt for 5 hr. The reaction was diluted with EtOAc (40 ml). The resulting organic solution was extracted with water (2×20 ml) and saturated NaCl (20 ml). The organic layer was dried over MgSO4, filtered and concentrated. The resulting residue was purified by silica gel column chromatography, (4 g silica gel) eluting with 20%-80% EtOAc/Hex to give product (R)-2-(benzyloxy)-N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide as a beige solid (70 mg, 76% yield).

Workup

  1. customprepared
  2. extractionThe resulting organic solution was extracted with water (2×20 ml) and saturated NaCl (20 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel column chromatography, (4 g silica gel)
  7. washeluting with 20%-80% EtOAc/Hex

Sources & evidence

ORD record
ord-c433ab247cf64754a8eb9fa9939d4c25
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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