Ethyl chloroformate → HCID 25230870, compound

HRID 657591Notes

Reaction equation

HRID 657591 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.Cl[C:42]([O:44][CH2:45][CH3:46])=[O:43]>C(Cl)Cl>[CH2:45]([O:44][C:42](=[O:43])[O:20][CH2:19][N:11]1[C:12](=[O:18])[C:13]([CH:15]([CH3:17])[CH3:16])=[CH:14][C:9]([O:8][C:7]2[C:6]([Cl:21])=[CH:5][C:4]([N:22]3[C:27](=[O:28])[NH:26][C:25](=[O:29])[C:24]([C:30]#[N:31])=[N:23]3)=[CH:3][C:2]=2[Cl:1])=[N:10]1)[CH3:46]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 25230624HCID 25230624, compound

Product 1

HCID 25230870HCID 25230870, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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), 4-N,N-dimethyaminopyridine (25.3 mg, 0.21 mmol), N,N-diisopropylethylamine (0.23 mL, 1.29 mmol), in methylene chloride (3 mL) at 0° C. was treated with ethyl chloroformate (45 μL, 0.47 mmol). The reaction was stirred at allowed to gradually warm to 25° C. and was stirred at 25° C. for 48 h. At this time, the reaction mixture was diluted with methylene chloride (100 mL) and was washed with water (3×100 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over magnesium sulfate, filtered, rinsed and concentrated in vacuo. ISCO CombiFlash chromatography (40 g, 1-10% methanol/methylene chloride) followed by reverse phase chromatography (Pursuit C-18 column, acetonitrile gradient with ammonium acetate) afforded carbonic 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 ethyl ester (89.9 mg, 39%) as a white solid. ES+-HRMS m/e calcd for C21H18N6O7Cl2 (M+H+) 537.0687, found 537.0686.

Workup

  1. stirringwas stirred at 25° C. for 48 h
  2. washwas washed with water (3×100 mL)
  3. washThe combined organics were washed with a saturated aqueous sodium chloride solution (1×100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. washrinsed
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8fad3cd4fe444d9fb35ee38e74c8ed57
Source dataset
uspto-grants-2011_12
Patent number
US08076334B2

Reaction notes

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