Methanol → 2-[(4-Fluorophenyl)methyl]-7,8-dihydro-10-hydroxy-8-methylpyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione

HRID 494105Notes

Reaction equation

HRID 494105 reaction equation
Br[C:2]1[C:3](=[O:24])[N:4]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[N:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[C:10](=[O:15])[CH2:9]1.C1(C(N)C2CCCCC2)CCCCC1.[CH3:39][OH:40]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][N:4]2[C:3](=[O:24])[C:2]3[C:39]([OH:40])=[C:9]4[C:10](=[O:15])[N:11]([CH3:14])[CH2:12][CH2:13][N:8]4[C:7]=3[CH:6]=[N:5]2)=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 10774245alpha-CyclohexylcyclohexanemethanamineHCID 68867528HCID 68867528, compound

Product 1

HCID 546779322-[(4-Fluorophenyl)methyl]-7,8-dihydro-10-hydroxy-8-methylpyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of 4-bromo-2-(4-fluorobenzyl)-5-(4-methyl-3-oxopiperazin-1-yl)pyridazin-3(2H)-one (0.2 g, 0.51 mmol), dicyclohexylmethylamine (0.15 g, 0.76 mmol), and bis-(tri-t-butylphosphine)palladium (0) (52 mg, 0.10 mmol) in anhydrous methanol (5 mL) was heated in a stainless steel pressure vessel under an atmosphere of carbon monoxide (250 psi) in an oil bath at 90° C. overnight. The resultant mixture was diluted with methanol, filtered through a pad of Celite. The filtrate was concentrated under vacuum. The residual oil was triturated with methanol. The white solid precipitated was filtered to provide the titled dione.

Workup

  1. filtrationfiltered through a pad of Celite
  2. concentrationThe filtrate was concentrated under vacuum
  3. customThe residual oil was triturated with methanol
  4. customThe white solid precipitated
  5. filtrationwas filtered
  6. customto provide the titled dione

Sources & evidence

ORD record
ord-1787552fdde342afbbc82afabdb147ec
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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