Sodium hydride → HCID 178504205, compound

HRID 1025582Notes

Reaction equation

HRID 1025582 reaction equation
[NH2:1][C:2]1[C:6]([C:7]#[N:8])=[CH:5][NH:4][N:3]=1.[H-].[Na+].Cl[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C>[CH3:17][Si:16]([CH2:15][CH2:14][O:13][CH2:12][C:5]1[C:6]([C:7]#[N:8])=[C:2]([NH2:1])[NH:3][N:4]=1)([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178510443HCID 178510443, compound

Product 1

HCID 178504205HCID 178504205, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-1H-pyrazole-4-carbonitrile (10 g, 92.5 mmol) was dissolved in 100 mL of DMF and the solution was stirred at 0° C. Sodium hydride (60% in mineral oil, 7.4 g, 185 mmol) was added in small portions. The mixture was stirred for 30 minutes and (2-(chloromethoxy)ethyl)trimethylsilane (90% purity, 17.1 g, 92.5 mmol) was added. The mixture was stirred at room temperature for 1 hr and then extracted with chloroform and aqueous ammonium chloride solution. The organic layer was washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was purified through ISCO flash column chromatography (220 g silica gel, ethyl acetate in hexanes 5% to 40% in 25 minutes). The fractions with a slightly larger Rf as the major component were evaporated and then crystallized from 7% ethyl acetate in hexanes to give a white crystalline pure compound as 1N-trimethylsilylethoxymethyl-5-amino-4-cyanopyrazole (3.75 g). The fractions with a slightly lower Rf as the major component were evaporated and then crystallized from 4% ethyl acetate in hexanes to give a pure crystalline compound as 1N-trimethylsilylethoxymethyl-3-amino-4-cyanopyrazole (3.50 g). The mother liquor and fractions containing both components were combined and evaporated to give a mixture (7.4 g, total yield for this step 67%). For 1N-trimethylsilylethoxymethyl-5-amino-4-cyanopyrazole: LC/MS calcd for C10H18N4OSi (m/e) 238.12, obsd 237.2 (M−H, ES−); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.00 (s, 9H), 0.82 (t, J=8.0 Hz, 2H), 3.53 (t, J=8.0 Hz, 2H), 5.24 (s, 2H) 6.80 (s, 2H) 7.58 (s, 1H); For 1N-trimethylsilylethoxymethyl-3-amino-4-cyanopyrazole: 1H NMR (400 MHz, DMSO-d6) δ ppm 0.00 (s, 9H), 0.83 (t, J=8.0 Hz, 2H), 3.51 (t, J=8.0 Hz, 2H), 5.15 (s, 2H), 5.65 (s, 2H), 8.28 (s, 1H).

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. stirringThe mixture was stirred at room temperature for 1 hr
  3. extractionextracted with chloroform and aqueous ammonium chloride solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified through ISCO flash column chromatography (220 g silica gel, ethyl acetate in hexanes 5% to 40% in 25 minutes)
  9. customThe fractions with a slightly larger Rf as the major component were evaporated
  10. customcrystallized from 7% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1e3c1fc3d91d45f6bb87bc240b057c4a
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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