Hydrochloric Acid → 3-amino-1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrazole-4-carbonitrile

HRID 1025651Notes

Reaction equation

HRID 1025651 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[C:17]([CH2:49][OH:50])=[C:18]([N:22]3[CH:26]=[C:25]([C:27]#[N:28])[C:24]([NH:29]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)=[N:23]3)[CH:19]=[CH:20][CH:21]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].CO.Cl>CCOCC>[NH2:29][C:24]1[C:25]([C:27]#[N:28])=[CH:26][N:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([N:10]3[N:9]=[CH:8][C:7]4[C:12](=[CH:13][CH:14]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[CH:6]=4)[C:11]3=[O:15])[C:17]=2[CH2:49][OH:50])[N:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 710084231-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-3-(tritylamino)-1H-pyrazole-4-carbonitrile

Product 1

HCID 710081183-amino-1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrazole-4-carbonitrileYield 74%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-3-(tritylamino)-1H-pyrazole-4-carbonitrile (382 mg 0.582 mmol) was dissolved in Et2O (30 mL) and cooled to 0° C. in. MeOH (2 mL) was added followed by saturated ethereal HCl (2 mL, prepared by bubbling HCl gas into 100 mL of ether). The reaction mixture was allowed to stir at 0° C. for 30 minutes, after which, it was judged to be complete by TLC. The volatiles were removed in vacuo and residue was partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL) and stirred vigorously. The aqueous layer was separated and extracted with EtOAc (50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The oily residue was bound to silica gel and the crude product was purified over a 25 g silica gel cartridge eluting the column with a 20-70% EtOAc/hexanes gradient to give 3-Amino-1-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-4-carbonitril (178 mg, 74%) as a white-powdery solid.

Workup

  1. customThe volatiles were removed in vacuo and residue
  2. customwas partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL)
  3. stirringstirred vigorously
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc (50 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthe crude product was purified over a 25 g silica gel cartridge
  10. washeluting the column with a 20-70% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-d3aedc3d36a541d3b9849dedc5ee83f6
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…