Sodium Bicarbonate → 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-formyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carbonitrile

HRID 1025587Notes

Reaction equation

HRID 1025587 reaction equation
[CH:1]([C:3]1[C:8](I)=[CH:7][CH:6]=[CH:5][C:4]=1[N:10]1[CH:14]=[C:13]([C:15]#[N:16])[C:12]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][CH:19]=2)=[N:11]1)=[O:2].[C:32]([C:36]1[CH:37]=[C:38]2[C:43](=[C:44]([F:46])[CH:45]=1)[C:42](=[O:47])[NH:41][N:40]=[CH:39]2)([CH3:35])([CH3:34])[CH3:33].C(=O)(O)[O-].[Na+]>CS(C)=O>[C:32]([C:36]1[CH:37]=[C:38]2[C:43](=[C:44]([F:46])[CH:45]=1)[C:42](=[O:47])[N:41]([C:8]1[C:3]([CH:1]=[O:2])=[C:4]([N:10]3[CH:14]=[C:13]([C:15]#[N:16])[C:12]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[O:25])=[CH:20][CH:19]=4)=[N:11]3)[CH:5]=[CH:6][CH:7]=1)[N:40]=[CH:39]2)([CH3:35])([CH3:33])[CH3:34]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-oneHCID 866737061-(2-Formyl-3-iodophenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile

Product 1

HCID 866737071-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-formyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carbonitrileYield 40%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1-(2-Formyl-3-iodophenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (115 mg, 0.218 mmol), 6-tert-butyl-8-fluorophthalazin-1(2H)-one (48 mg, 0.218 mmol), cuprous iodide (41.5 mg, 0.218 mmol) and sodium bicarbonate (36.6 mg, 0.436 mmol) were combined in 2 mL of DMSO. The mixture was thoroughly degassed with argon and stirred in an oil bath preheated to 100° C. for 1 hr. The mixture was extracted with dichloromethane and water. The organic layer was washed with brine, dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified by flash column chromatography using methanol in dichloromethane (0% to 5% in 16 minutes, 24 g silica gel) to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-formyl-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carbonitrile as a pale pink solid (54 mg, 40% yield). LC/MS clacd for C34H30FN7O4 (m/e) 619.23, obsd 620.0 (M+H, ES+); 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 9H), 3.56-3.76 (m, 8H), 6.61 br. s., 1H), 7.40 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.6 Hz, 2H), 7.52 (dd, J=12.4, 1.8 Hz, 1H), 7.55-7.59 (m, 2H), 7.64 (d, J=7.8 Hz, 1H), 7.78 (t, J=8.1 Hz, 1H), 8.16 (s, 1H), 8.32 (s, 1H), 9.97 (s, 1H).

Workup

  1. customThe mixture was thoroughly degassed with argon
  2. extractionThe mixture was extracted with dichloromethane and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customSolvents were evaporated
  7. customthe residue was purified by flash column chromatography
  8. custommethanol in dichloromethane (0% to 5% in 16 minutes, 24 g silica gel)

Sources & evidence

ORD record
ord-61153b996af74458a744fd282c1ebf50
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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