Acetyl chloride → HCID 25230625, compound

HRID 657585Notes

Reaction equation

HRID 657585 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(N(CC)C(C)C)(C)C.[C:41](Cl)(=[O:43])[CH3:42]>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:41](=[O:43])[CH3:42])[N:10]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 25230624HCID 25230624, compound

Product 1

HCID 25230625HCID 25230625, compoundYield 21%

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, 0.43 mmol), N,N-diisopropylethylamine (0.23 mL, 1.29 mmol) and 4-N,N-dimethylaminopyridine (25.8 mg, 0.21 mmol) in methylene chloride (3.0 mL) cooled to 0° C. was treated with acetyl chloride (33.5 μL, 0.47 mmol). The reaction mixture was warmed to 25° C. over 3.5 h. The reaction mixture was then warmed to 40° C. and stirred overnight. At this time, the reaction mixture was cooled to 25° C. and then partitioned between methylene chloride (100 mL) and water (100 mL). The organics were then washed with a 1N aqueous hydrochloric acid solution (3×100 mL), water (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. ISCO CombiFlash chromatography (40 g, 0.5-4.0% methanol/methylene chloride) afforded acetic acid 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 (45.9 mg, 21%) as a yellow solid. ES+-HRMS m/e calcd for C20H16N6O6Cl2 (M+H+) 507.0581, found 507.0582.

Workup

  1. temperatureThe reaction mixture was then warmed to 40° C.
  2. temperatureAt this time, the reaction mixture was cooled to 25° C.
  3. custompartitioned between methylene chloride (100 mL) and water (100 mL)
  4. washThe organics were then washed with a 1N aqueous hydrochloric acid solution (3×100 mL), water (1×100 mL)
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. washrinsed
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7e3db91998b24dbdba5b6cfac0024f22
Source dataset
uspto-grants-2011_12
Patent number
US08076334B2

Reaction notes

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