Ammonium Chloride → 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-3-carboxylic acid amide

HRID 1025610Notes

Reaction equation

HRID 1025610 reaction equation
Br[C:2]1[C:3]([CH:15]=[O:16])=[C:4]([N:8]2[CH:12]=[CH:11][C:10]([C:13]#[N:14])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[C:17]([C:21]1[CH:22]=[C:23]2[C:28](=[C:29]([F:31])[CH:30]=1)[C:27](=[O:32])[NH:26][N:25]=[CH:24]2)([CH3:20])([CH3:19])[CH3:18].C(=O)(O)[O-:34].[Na+].[NH4+].[Cl-]>[Cu]I.CS(C)=O>[C:17]([C:21]1[CH:22]=[C:23]2[C:28](=[C:29]([F:31])[CH:30]=1)[C:27](=[O:32])[N:26]([C:2]1[C:3]([CH2:15][OH:16])=[C:4]([N:8]3[CH:12]=[CH:11][C:10]([C:13]([NH2:14])=[O:34])=[N:9]3)[CH:5]=[CH:6][CH:7]=1)[N:25]=[CH:24]2)([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-oneHCID 866737201-(3-bromo-2-formylphenyl)-1H-pyrazole-3-carbonitrile

Product 1

HCID 710084691-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-3-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

In a 25 mL container, 1-(3-bromo-2-formylphenyl)-1H-pyrazole-3-carbonitrile (50 mg, 181 μmol, Eq: 1.00), 6-tert-butyl-8-fluorophthalazin-1(2H)-one (79.8 mg, 362 μmol, Eq: 2) and copper (I) iodide (69.0 mg, 362 μmol, Eq: 2.00) were combined with DMSO (2.00 ml) to give a yellow suspension. Sodium bicarbonate (38.0 mg, 453 μmol, Eq: 2.5) was added to it. The mixture was heated in a microwave at 120° C. for 1 hr. The reaction mixture was poured into 25 mL sat NH4Cl and extracted with EtOAc (3×25 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The organic layer was concentrated and purified through ISCO flash column chromatography using ethyl acetate (containing 5% methanol) in hexanes (5% to 80% linear gradient in 15 minutes, 12 g silica gel) to give the pure desired product which was triturated with ether in hexanes and filtered to obtain 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-1H-pyrazole-3-carbonitrile (19 mg, 25%).

Workup

  1. customto give a yellow suspension
  2. additionThe reaction mixture was poured into 25 mL
  3. extractionextracted with EtOAc (3×25 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. concentrationThe organic layer was concentrated
  7. custompurified through ISCO flash column chromatography
  8. customethyl acetate (containing 5% methanol) in hexanes (5% to 80% linear gradient in 15 minutes, 12 g silica gel)

Sources & evidence

ORD record
ord-da85750c771441ff920817c320c57050
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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