Succinic anhydride → HCID 25230749, compound

HRID 657586Notes

Reaction equation

HRID 657586 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:5]=[C:6]([Cl:21])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH2:19][OH:20])[N:10]=1.[C:32]1(=[O:38])[O:37][C:35](=[O:36])[CH2:34][CH2:33]1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>C(Cl)Cl>[Cl:21][C:6]1[CH:5]=[C:4]([N:22]2[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH2:19][O:20][C:32](=[O:38])[CH2:33][CH2:34][C:35]([OH:37])=[O:36])[N:10]=1

Participants

6

Reactant 4

HCID 7922Succinic anhydrideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 25230624HCID 25230624, compound

Product 1

HCID 25230749HCID 25230749, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-[3,5-dichloro-4-(1-hydroxymethyl-5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (200 mg, 0.42 mmol), 4-N,N-dimethyaminopyridine (2.6 mg, 0.02 mmol) and succinic anhydride (47 mg, 0.47 mmol) in methylene chloride (2.53 mL) at 25° C. was treated with N,N-diisopropylethylamine (0.17 mL, 0.98 mmol). The reaction mixture was stirred at 25° C. for 3.5 h. At this time, the reaction mixture was poured onto a saturated aqueous ammonium chloride solution (100 mL) and was then extracted with a 90/10 methylene chloride/methanol solution (3×100 mL). The pH of the aqueous layer was brought to pH=2 with a few drops of a 2N aqueous hydrochloric acid solution and was then extracted with a 90/10 methylene chloride/methanol solution (1×100 mL). The combined organics were dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. ISCO CombiFlash chromatography (12 g, 0.5-4% methanol/methylene chloride) followed by supercritical fluid chromatography (Daicel OJ column, 30% methanol) afforded succinic acid mono-{3-[2,6-dichloro-4-(6-cyano-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-5-isopropyl-6-oxo-6H-pyridazin-1-ylmethyl}ester (57 mg, 24%) as a light tan solid. ES+-HRMS m/e calcd for C22H18N6O8Cl2 (M+H+) 565.0636, found 565.0633.

Workup

  1. extractionwas then extracted with a 90/10 methylene chloride/methanol solution (3×100 mL)
  2. extractionwas then extracted with a 90/10 methylene chloride/methanol solution (1×100 mL)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. washrinsed
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-669b6ca8538d486486f5b1dc917ef14b
Source dataset
uspto-grants-2011_12
Patent number
US08076334B2

Reaction notes

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