Sodium Acetate → 1,2-Diethyl 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1,2-pyridazinedicarboxylate

HRID 75172Notes

Reaction equation

[NH2:1][C:2](=[S:19])[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:4]1.Br[CH2:21][C:22]([C:24]1[CH2:28][CH:27]([C:29]2[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:30]=2[F:36])[O:26][N:25]=1)=O.C([O-])(=O)C.[Na+]>CO>[F:36][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]([F:35])[C:29]=1[CH:27]1[O:26][N:25]=[C:24]([C:22]2[N:1]=[C:2]([CH:3]3[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:4]3)[S:19][CH:21]=2)[CH2:28]1

Participants

Conditions

Temperature: 35 °C

Procedure

A mixture of 1,2-diethyl 4-(aminothioxomethyl)tetrahydro-1,2-pyridazinedicarboxylate (i.e. the product of Step F) (2.58 g, 0.0089 mol) and 2-bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (i.e the product of Step C) (2.63 g, 0.0086 mol) in methanol (20 mL) were carefully heated to 35° C. No exotherm was observed and the temperature was raised to between 45 to 50° C. and held at this temperature for 1 h. The reaction mixture was neutralised with aqueous sodium acetate (0.73 g in about 20 mL water). The reaction mixture was extracted with diethyl ether (3×), dried magnesium sulfate, filtered, and concentrated under reduced pressure to provide the title compound (4.18 g), which was used without purification.

Workup

temperaturethe temperature was raised to between 45 to 50° C.
extractionThe reaction mixture was extracted with diethyl ether (3×), dried magnesium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-ff949c2df7874969a9d53c14b01d5ec4
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835427B2

Reaction notes

Loading…