Triethylamine → HCID 90004995, compound

HRID 1771398Notes

Reaction equation

HRID 1771398 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.C(N(CC)CC)C.[OH:18][C:19]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=2)[N:21]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[N:20]=1.C([O-])(O)=O.[Na+]>C(#N)C>[O:8]1[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][O:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=3)[N:21]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[N:20]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)2×HCID 516892Sodium BicarbonateHCID 178473418HCID 178473418, compound

Product 1

HCID 90004995HCID 90004995, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(2-chloroethyl)morpholine hydrochloride (390 mg, 2.10 mmol) in acetonitrile (25 mL) was added triethylamine (0.56 mL, 4.0 mmol) and ethyl 3-hydroxy-5-nitro-1H-indazole-1-carboxylate (563 mg, 1.91 mmol) and the mixture heated to reflux for 2 days. Additional portions of 4-(2-chloroethyl)morpholine hydrochloride (178 mg, 0.955 mmol) and triethylamine (130 μL, 0.95 mmol) were added and the reaction mixture was heated at reflux for a further 3 hr and then cooled to RT. Saturated aq. NaHCO3 (50 mL) was added and the mixture was extracted with EtOAc (2×100 mL). The organic extracts were combined, dried and evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 40 g, 0-100% EtOAc in isohexane, gradient elution) to afford ethyl 3-(2-morpholinoethoxy)-5-nitro-1H-indazole-1-carboxylate as a yellow solid (294 mg, 41%); Rt 1.26 min (Method 2, acidic); m/z 365 (M+H)+ (ES+).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2 days
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for a further 3 hr
  5. extractionthe mixture was extracted with EtOAc (2×100 mL)
  6. customdried
  7. customevaporated in vacuo
  8. customthe residue was purified by flash column chromatography (SiO2, 40 g, 0-100% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-e301b53bfa6d4043b82c87ed7549b7b2
Source dataset
uspto-grants-2016_02
Patent number
US09249125B2

Reaction notes

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