Water → HCID 178436450, compound

HRID 1754067Notes

Reaction equation

HRID 1754067 reaction equation
[CH:1]1([NH:6][C:7]2[N:11]3[N:12]=[CH:13][C:14]([C:15]#[N:16])=[C:10]3[NH:9][C:8]=2[C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH3:24])=[CH:19][CH:18]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH2:25]>CS(C)=O>[NH2:9][C:10]1[N:11](/[C:7](=[N:6]/[CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)/[C:8]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH3:24])=[CH:19][CH:18]=2)=[O:25])[N:12]=[CH:13][C:14]=1[C:15]#[N:16]

Participants

4

Reactant 2

HCID 962WaterHCID 178435864HCID 178435864, compound

Product 1

HCID 178436450HCID 178436450, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A light brown solution of 3-(cyclopentylamino)-2-(4-ethylphenyl)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile (56.4 mg, 0.177 mmol) in DMSO (17.7 mL) was stored for 35 days at RT. Within 24 h, it became a dark brown solution. After 35 days, LCMS analysis indicated the absence of starting material and the presence of a strong desired peak. Then, it was poured into water (1 L) and the resulting cloudy brown solution was extracted with EA (2×200 mL). Then, the combined extracts were washed with water and brine solution (2 L) to wash the DMSO. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated to give the red brown paste which was purified using an ISCO (120 g) column chromatography eluting with 0-40% ethyl acetate in hexanes. The desired fractions were combined and the solvent was removed under vacuum to obtain 5.9 mg (10% yield) of (E)-5-amino-1-(1-(cyclopentylimino)-2-(4-ethylphenyl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile as an off-white solid. 1H NMR (400 MHz, CDCl3) δ: 1.28 (t, J=7.7 Hz, 3H), 1.40-2.00 (br m, 8H), 2.75 (q, J=7.7 Hz, 2H), 3.78 (p, J=6.1 Hz, 1H), 6.78 (br s, 2H), 7.36 (d, J=8.3 Hz, 2H), 7.42 (s, 1H), 7.81 (d, J=8.3 Hz, 2H). LC/MS calcd. for C19H21N5O3 (m/e) 367.4, obsd. 368.0 (M+H, ES+).

Workup

  1. waitAfter 35 days
  2. extractionthe resulting cloudy brown solution was extracted with EA (2×200 mL)
  3. washThen, the combined extracts were washed with water and brine solution (2 L)
  4. washto wash the DMSO
  5. dry with materialThe organic layer was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the red brown paste which
  9. customwas purified
  10. washeluting with 0-40% ethyl acetate in hexanes
  11. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-a8f23d1847c14e54899b1cf06fba1cfa
Source dataset
uspto-grants-2015_10
Patent number
US09169215B2

Reaction notes

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