Methanol → Ethyl 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydropyrido[2,3-d]pyridazine-3-carboxylate

HRID 1947256Notes

Reaction equation

HRID 1947256 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:17](=[O:19])[NH:16][N:15]=[CH:14][C:13]=3[NH:12][C:11]([CH3:20])=[C:10]2[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:5]([O:26][CH3:27])[CH:4]=1)#[N:2].ClCCl.F[B-](F)(F)F.[CH2:36]([O+](CC)CC)[CH3:37].CO>O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][N:15]=[N:16][C:17]=3[O:19][CH2:36][CH3:37])[NH:12][C:11]([CH3:20])=[C:10]2[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:5]([O:26][CH3:27])[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 2723982Triethyloxonium tetrafluoroborateHCID 42604983HCID 42604983, compound

Product 1

HCID 24856432Ethyl 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydropyrido[2,3-d]pyridazine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

50 mg (0.136 mmol) of ethyl 4-(4-cyano-2-methoxyphenyl)-2-methyl-5-oxo-1,4,5,6-tetrahydropyrido[2,3-d]pyridazine-3-carboxylate are mixed under an argon atmosphere with 5 ml of abs. dichloromethane and 51.8 mg (0.273 mmol) of triethyloxonium tetrafluoroborate. After a reaction time of 2 hours at room temperature, the mixture is mixed with 5 ml of methanol and 0.5 ml of water and again stirred for 1 h. It is then diluted with 20 ml of water and extracted three times with dichloromethane. The combined organic phases are dried with magnesium sulfate, and the solvent is removed in a rotary evaporator. The residue is purified by preparative HPLC (eluent:acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5). 15 mg (27.8% of theory) of the title compound are obtained.

Workup

  1. extractionextracted three times with dichloromethane
  2. dry with materialThe combined organic phases are dried with magnesium sulfate
  3. customthe solvent is removed in a rotary evaporator
  4. customThe residue is purified by preparative HPLC (eluent:acetonitrile/water with 0.1% formic acid, gradient 20:80→95:5)

Sources & evidence

ORD record
ord-0b0feab56e5646c3a4e99d619428866b
Source dataset
uspto-grants-2013_03
Patent number
US08399471B2

Reaction notes

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