Methoxyacetyl chloride → 8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid N-isopropyl-N'-(2-methoxy-acetyl)-hydrazide

HRID 708287Notes

Reaction equation

HRID 708287 reaction equation
Cl.[CH:2]([N:5]([C:7]([C:9]1[S:10][C:11]2[CH2:12][CH2:13][O:14][C:15]3[CH:22]=[C:21]([Br:23])[CH:20]=[CH:19][C:16]=3[C:17]=2[N:18]=1)=[O:8])[NH2:6])([CH3:4])[CH3:3].[CH3:24][O:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[CH:2]([N:5]([C:7]([C:9]1[S:10][C:11]2[CH2:12][CH2:13][O:14][C:15]3[CH:22]=[C:21]([Br:23])[CH:20]=[CH:19][C:16]=3[C:17]=2[N:18]=1)=[O:8])[NH:6][C:27](=[O:28])[CH2:26][O:25][CH3:24])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 96623Methoxyacetyl chlorideHCID 670506528-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid N-isopropyl-hydrazide hydrochloride

Product 1

HCID 582038628-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid N-isopropyl-N'-(2-methoxy-acetyl)-hydrazide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid N-isopropyl-hydrazide hydrochloride (3.5 g, 8.4 mmol) and TEA (4.07 mL, 29.3 mmol) in DCM (35 mL) at 0° C. was added methoxy-acetyl chloride (1.53 mL, 16.7 mmol) dropwise and the reaction mixture was stirred at 0° C. for 0.75 h then 18 h at RT. The reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution and the phases separated. The aqueous phase was extracted with DCM (×2) before the combined organic extracts were washed with 10% citric acid solution, followed by brine then dried (Na2SO4) and concentrated in vacuo to give a yellow brown solid. The solid was triturated with diethyl ether to give the title compound as an off white solid (2.66 g, 5.86 mmol, 70%). LCMS RT=4.64 min, [M+H]+=454/456.

Workup

  1. custom18 h
  2. customat RT
  3. customThe reaction was quenched by the addition of saturated aqueous sodium bicarbonate solution
  4. customthe phases separated
  5. extractionThe aqueous phase was extracted with DCM (×2) before the combined organic extracts
  6. washwere washed with 10% citric acid solution
  7. dry with materialthen dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto give a yellow brown solid
  10. customThe solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-43949ee968a149cb910001acfda59ce6
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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