Stannous chloride dihydrate → HCID 58851477, compound

HRID 1696499Notes

Reaction equation

HRID 1696499 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:4][CH:3]=1.[N:17]([O-])=O.[Na+].O.O.Cl[Sn]Cl.[C:26]([CH2:32][C:33]#[N:34])(=O)[C:27]([CH3:30])([CH3:29])[CH3:28]>Cl.O>[NH2:34][C:33]1[N:1]([C:2]2[CH:10]=[C:9]3[C:5]([CH2:6][CH2:7][N:8]3[C:11](=[O:16])[C:12]([F:15])([F:13])[F:14])=[CH:4][CH:3]=2)[N:17]=[C:26]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:32]=1

Participants

7

Reactant 4

HCID 61436Stannous chloride dihydrateHCID 108871Pentanenitrile, 4,4-dimethyl-3-oxo-HCID 10823326HCID 10823326, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 58851477HCID 58851477, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of 1-(6-aminoindolin-1-yl)-2,2,2-trifluoroethanone (7.00 g, 30.4 mmol) in 6N HCl (50 mL) was dropwise added a solution of NaNO2 (2.10 g, 30.4 mmol) in H2O (5 mL). The resulting slurry was stirred at 0° C. for 30 min. A solution of SnCl2.2H2O (11.5 g, 60.8 mmol) in conc. HCl (60 mL) was added dropwise and after the addition was complete the resulting slurry was stirred at RT for 2 h. The mixture was filtered and the resulting solid was redissolved in EtOH (200 mL). Pivaloyl acetonitrile (4.57 g, 36.5 mmol) was added and the solution was heated at reflux overnight. Water (100 mL) was added and the mixture was extracted with CH2Cl2 (3×100 mL), dried (MgSO4), concentrated and purified by recrystallization from ethyl acetate/hexanes to yield 1-(6-(5-amino-3-t-butyl-1 H-pyrazol-1-yl)indolin-1-yl)-2,2,2-trifluoroethanone (3.2 g, 30% yield) as a light-brown solid. 1H-NMR (400 MHz, acetone-d6): δ 8.49 (d, J=2.0 Hz, 1H), 7.51 (dd, J=8.4, and 2.0 Hz, 1H), 4.41 (t, J=8.2 Hz, 2H), 3.32 (t, J=8.2 Hz, 2H), 1.32 (s, 9H), pyrazolamine protons not observed; MS (ESI) m/z: 353.2 (M+H+).

Workup

  1. additionafter the addition
  2. stirringwas stirred at RT for 2 h
  3. filtrationThe mixture was filtered
  4. dissolutionthe resulting solid was redissolved in EtOH (200 mL)
  5. temperaturethe solution was heated
  6. temperatureat reflux overnight
  7. extractionthe mixture was extracted with CH2Cl2 (3×100 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. custompurified by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-2eea0b9faf4141abbcd9a6fc498a9374
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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