Sodium Nitrite → N-(3-Amino-2-tert-butyl-1H-indol-5-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 503450Notes

Reaction equation

HRID 503450 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[NH:21][C:20]([C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[N:29]([O-])=O.[Na+]>CC(O)=O.O>[NH2:29][C:19]1[C:18]2[C:22](=[CH:23][CH:24]=[C:16]([NH:15][C:13]([C:10]3([C:8]4[CH:7]=[CH:6][C:5]5[O:1][CH2:2][O:3][C:4]=5[CH:9]=4)[CH2:12][CH2:11]3)=[O:14])[CH:17]=2)[NH:21][C:20]=1[C:25]([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 2

HCID 23668193Sodium NitriteHCID 247629031-(Benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropanecarboxamide

Product 1

HCID 59129316N-(3-Amino-2-tert-butyl-1H-indol-5-yl)-1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-1H-indol-5-yl)cyclopropane carboxamide (50 mg, 0.13 mmol) was dissolved in AcOH (2 mL) and warmed to 45° C. To the mixture was added a solution of NaNO2 (9 mg) in H2O (0.03 mL). The mixture was allowed to stir for 30 min at 45° C. before the precipitate was collected and washed with Et2O. This material was used in the next step without further purification. To the crude material, 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-3-nitroso-1H-indol-5-yl)cyclopropanecarboxamide, was added AcOH (2 mL) and Zn dust (5 mg). The mixture was allowed to stir for 1 h at ambient temperature. EtOAc and H2O were added to the mixture. The layers were separated and the organic layer washed with sat. aq. NaHCO3, dried over MgSO4, and concentrated in vacuo. The residue was taken up in DMF (1 mL) and was purified using prep-HPLC. LCMS: m/z 392.3; retention time of 2.18 min.

Workup

  1. customwas collected
  2. washwashed with Et2O
  3. customThis material was used in the next step without further purification
  4. additionTo the crude material, 1-(benzo[d][1,3]dioxol-5-yl)-N-(2-tert-butyl-3-nitroso-1H-indol-5-yl)cyclopropanecarboxamide, was added AcOH (2 mL) and Zn dust (5 mg)
  5. stirringto stir for 1 h at ambient temperature
  6. additionEtOAc and H2O were added to the mixture
  7. customThe layers were separated
  8. washthe organic layer washed with sat. aq. NaHCO3
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customwas purified

Sources & evidence

ORD record
ord-219f9eb9a54e4bd18f6dbbd2ec41aba0
Source dataset
uspto-grants-2010_08
Patent number
US07776905B2

Reaction notes

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