Hydrazine, ethyl-, ethanedioate (1:1) → 4-{(4R)-7-Ethyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-d]-pyridazin-4-yl}benzonitrile

HRID 2039699Notes

Reaction equation

Br[CH2:2][C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7](=[O:19])[NH:6][C@H:5]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)[C:4]=1[C:28](OCC)=[O:29].C(O)(=O)C(O)=O.[CH2:39]([NH:41][NH2:42])[CH3:40]>O1CCOCC1>[CH2:39]([N:41]1[CH2:2][C:3]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=3)[C:7](=[O:19])[NH:6][C@H:5]([C:20]3[CH:21]=[CH:22][C:23]([C:26]#[N:27])=[CH:24][CH:25]=3)[C:4]=2[C:28](=[O:29])[NH:42]1)[CH3:40]

Participants

Conditions

Temperature: 120 °C

Procedure

200 mg (0.393 mmol) of ethyl (4R)-6-(bromomethyl)-4-(4-cyanophenyl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (Example 6A) were dissolved in 1 ml of dioxane, 71 mg (0.472 mmol) of ethylhydrazine oxalate were added and the mixture was stirred at 120° C. for 3 hours. The reaction mixture was then concentrated, and the residue that remained was purified by preparative HPLC (Method 10). The product fractions were combined and concentrated, and the solid that remained was dried under reduced pressure (Yield: 26.0 mg, 15% of theory).

Workup

concentrationThe reaction mixture was then concentrated
customthe residue that remained was purified by preparative HPLC (Method 10)
concentrationconcentrated
customthe solid that remained was dried under reduced pressure (Yield: 26.0 mg, 15% of theory)

Sources & evidence

ORD record: ord-fcec8e57cbe744c8ae6a98d8c37b15ec
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580800B2

Reaction notes

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