HCID 118389360, compound → HCID 76317518, compound

HRID 925126Notes

Reaction equation

HRID 925126 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:17][CH2:18][CH2:19][CH2:20][N:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:5][C:6]([N+:14]([O-])=O)=[C:7]([C:9]([CH3:13])([CH3:12])[C:10]#[N:11])[CH:8]=1>CC(O)=O.[Zn]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]2[C:6](=[CH:5][C:4]=1[O:17][CH2:18][CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[N:14]=[C:10]([NH2:11])[C:9]2([CH3:13])[CH3:12]

Participants

4

Reactant 1

HCID 118389360HCID 118389360, compound

Product 1

HCID 76317518HCID 76317518, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

2-(5-Methoxy-2-nitro-4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-2-methylpropanenitrile (5.61 g, 16.15 mmol), from Step 1, in AcOH (100 mL) was treated with zinc (10.56 g, 161 mmol). The reaction was stirred at 90° C. for 30 min, filtered, and concentrated to dryness. The dried residue was taken into 4:1 THF:DCM and washed with saturated aqueous sodium bicarbonate solution. Aqueous washings were back-extracted with THF:DCM mixture 5 times. Organic layers were combined, dried (MgSO4), filtered and concentrated. Purification by flash chromatography (silica gel, 15-25% 1N methanolic ammonia/dichloromethane) afforded 4.95 g (97%) of 5-methoxy-3,3-dimethyl-6-(3-(pyrrolidin-1-yl)propoxy)-3H-indol-2-amine 1H NMR (400 MHz, METHANOL-D4) δ 7.17 (s, 1H), 6.90 (s, 1H), 4.16 (t, J=5.5 Hz, 2H), 3.87 (s, 3H), 3.85-3.73 (m, 2H), 3.46 (t, J=7.1 Hz, 2H), 3.13 (dt, J=10.5, 7.7 Hz, 2H), 2.31-2.23 (m, 2H), 2.19 (dd, J=14.3, 7.6 Hz, 2H), 2.12-1.99 (m, 2H), 1.55 (s, 6H); MS (ESI) m/z 318 (M+H)+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated to dryness
  3. washDCM and washed with saturated aqueous sodium bicarbonate solution
  4. extractionAqueous washings were back-extracted with THF
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography (silica gel, 15-25% 1N methanolic ammonia/dichloromethane)

Sources & evidence

ORD record
ord-7ccfa0c06678480c9355d7a55f7b7ae8
Source dataset
uspto-grants-2016_03
Patent number
US09284272B2

Reaction notes

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