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

HRID 1629342Notes

Reaction equation

HRID 1629342 reaction equation
Cl.Cl.[CH:3]([N:6]([C:8]([C:10]1[N:19]=[C:18]2[N:12]([CH2:13][CH2:14][O:15][C:16]3[CH:23]=[C:22]([Br:24])[CH:21]=[CH:20][C:17]=32)[CH:11]=1)=[O:9])[NH2:7])([CH3:5])[CH3:4].[CH3:25][O:26][CH2:27][C:28](Cl)=[O:29]>C(Cl)Cl>[CH:3]([N:6]([C:8]([C:10]1[N:19]=[C:18]2[N:12]([CH2:13][CH2:14][O:15][C:16]3[CH:23]=[C:22]([Br:24])[CH:21]=[CH:20][C:17]=32)[CH:11]=1)=[O:9])[NH:7][C:28](=[O:29])[CH2:27][O:26][CH3:25])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 96623Methoxyacetyl chlorideHCID 670507018-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid N-isopropyl-hydrazide dihydrochloride

Product 1

HCID 582046368-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid N-isopropyl-N'-(2-methoxy-acetyl)-hydrazideYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 8-bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid N-isopropyl-hydrazide dihydrochloride (2.69 g, 6.1 mmol) in DCM (61 mL) was treated with TEA (3.84 mL, 27.6 mmol). The resultant solution was cooled to 0° C. before methoxyacetyl chloride (1.12 mL, 12.3 mmol) was added dropwise and the reaction stirred at 0° C. for 1.75 h. The reaction was quenched with saturated sodium bicarbonate solution and the phases separated. The aqueous phase was extracted with DCM (×2) before the combined organic phases were washed sequentially with 10% citric acid solution, saturated sodium bicarbonate solution and brine. The organic solution was dried (Na2SO4), concentrated in vacuo and the resultant solid was triturated with diethyl ether to give 8-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid N-isopropyl-N′-(2-methoxy-acetyl)-hydrazide as an off-white solid (2.29 g, 5.24 mmol, 86%). LCMS RT=4.29 min, [M+H]+=437/439. 1H NMR 400 MHz (DMSO-d) δ: 9.61 (1 H, s), 8.29 (1 H, d, J=8.63 Hz), 7.71 (1 H, s), 7.27 (1 H, dd, J=8.64, 2.06 Hz), 7.21 (1 H, d, J=2.06 Hz), 4.84 (1 H, t, J=6.91 Hz), 4.45 (4 H, s), 3.92 (2 H, s), 3.33 (3 H, s), 1.15 (6 H, d, J=6.66 Hz)

Workup

  1. additionwas added dropwise
  2. customThe reaction was quenched with saturated sodium bicarbonate solution
  3. customthe phases separated
  4. extractionThe aqueous phase was extracted with DCM (×2) before the combined organic phases
  5. washwere washed sequentially with 10% citric acid solution, saturated sodium bicarbonate solution and brine
  6. dry with materialThe organic solution was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customthe resultant solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-0ecdb50921dc4f9daedf4ffca5bc2a16
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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