Methanol → HCID 24856431, compound

HRID 1947255Notes

Reaction equation

HRID 1947255 reaction equation
[C:1]([C:4]1[CH:5]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=2[O:24][CH3:25])[C:6]2[C:11](=[O:12])[NH:10][N:9]=[CH:8][C:7]=2[NH:13][C:14]=1[CH3:15])(=[O:3])[CH3:2].ClCCl.F[B-](F)(F)F.[CH2:34]([O+](CC)CC)[CH3:35].CO>O>[C:1]([C:4]1[CH:5]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=2[O:24][CH3:25])[C:6]2[C:7]([NH:13][C:14]=1[CH3:15])=[CH:8][N:9]=[N:10][C:11]=2[O:12][CH2:34][CH3:35])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 2723982Triethyloxonium tetrafluoroborate2×HCID 68716227HCID 68716227, compound

Product 1

HCID 24856431HCID 24856431, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

65 mg (0.193 mmol) of 4-(3-acetyl-2-methyl-5-oxo-1,4,5,6-tetrahydropyrido[2,3-d]pyridazin-4-yl)-3-methoxybenzonitrile are mixed under an argon atmosphere with 4 ml of abs. dichloromethane and 73.4 mg (0.386 mmol) of triethyloxonium tetrafluoroborate. After a reaction time of 2 hours at room temperature (reaction check by HPLC), conversion remains incomplete. Two further equivalents of triethyloxonium tetrafluoroborate are added. After a further reaction time of 3 h, the mixture is mixed with 5 ml of methanol and 0.5 ml of water and again stirred for 2 h. It is then diluted with 20 ml of water and extracted three times with dichloromethane. The combined organic phases are dried with sodium 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). 8 mg (11.3% of theory) of the title compound are obtained.

Workup

  1. customAfter a reaction time of 2 hours at room temperature (reaction check by HPLC), conversion
  2. extractionextracted three times with dichloromethane
  3. dry with materialThe combined organic phases are dried with sodium sulfate
  4. customthe solvent is removed in a rotary evaporator
  5. 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-32e40a39b7f6403eabfe1700b860763a
Source dataset
uspto-grants-2013_03
Patent number
US08399471B2

Reaction notes

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