Sodium Bicarbonate → 1-(3-(6-tert-Butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]pyrazole-4-carbonitrile

HRID 1025584Notes

Reaction equation

HRID 1025584 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](=[CH:44][CH:45]=1)[C:42](=[O:46])[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](=[CH:44][CH:45]=1)[C:42](=[O:46])[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 576339336-(tert-butyl)phthalazin-1(2H)-oneHCID 866737061-(2-Formyl-3-iodophenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile

Product 1

HCID 866737051-(3-(6-tert-Butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]pyrazole-4-carbonitrileYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1-(2-Formyl-3-iodophenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (71 mg, 0.135 mmol), 6-tert-butylphthalazin-1(2H)-one (27.2 mg, 0.135 mmol), cuprous iodide (25.6 mg, 0.135 mmol) and sodium bicarbonate (22.6 mg, 0.269 mmol) were combined in 2 mL of DMSO. The mixture was thoroughly degassed with argon and then stirred in an oil bath preheated to 100° C. After 1 hr, the mixture was extracted with dichloromethane and water. The organic layer was dried over sodium sulfate and filtered. Solvents were evaporated and the residue was purified by flash column chromatography (12 g silica gel, 0% to 5% methanol in dichloromethane) to give 1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-3-[4-(morpholine-4-carbonyl)phenylamino]-1H-pyrazole-4-carbonitrile as a pale pink solid (34 mg, 42% yield). LC/MS clacd for C34H31N7O4 (m/e) 601.24, obsd 602.1 (M+H, ES+); 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (s, 9H), 3.68 (br. m., 8H), 6.68 (br. s., 1H), 7.39 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.6 Hz, 2H), 7.57 (dd, J=8.0, 1.1 Hz, 1H), 7.65-7.74 (m, 1H), 7.74-7.81 (m, 2H), 7.93 (dd, J=8.6, 1.8 Hz, 1H), 8.17 (s, 1H), 8.40 (d, J=8.6 Hz, 1H), 8.47 (br. s., 1H), 9.90 (br. s., 1H).

Workup

  1. customThe mixture was thoroughly degassed with argon
  2. custompreheated to 100° C
  3. extractionthe mixture was extracted with dichloromethane and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customSolvents were evaporated
  7. customthe residue was purified by flash column chromatography (12 g silica gel, 0% to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-80a681f4a20e4b1786b3138b66ae421e
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

Loading…