Sodium Bicarbonate → HCID 71008252, compound

HRID 1025590Notes

Reaction equation

HRID 1025590 reaction equation
Br[C:2]1[C:3](C=O)=[C:4]([N:8]2[CH:12]=[C:11]([C:13]#[N:14])[C:10]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[O:23])=[CH:18][CH:17]=3)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[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-:49].[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:2]1[CH:3]=[C:4]([N:8]3[CH:12]=[C:11]([C:13]([NH2:14])=[O:49])[C:10]([NH:15][C:16]4[CH:21]=[CH:20][C:19]([C:22]([N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)=[O:23])=[CH:18][CH:17]=4)=[N:9]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 86673708HCID 86673708, compound

Product 1

HCID 71008252HCID 71008252, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

1-(3-Bromo-2-formylphenyl)-3-(4-(morpholine-4-carbonyl)phenylamino)-1H-pyrazole-4-carbonitrile (34 mg, 0.0708 mmol), 6-tert-butyl-8-fluorophthalazin-1(2H)-one (31.2 mg, 0.142 mmol), cuprous iodide (27 mg, 0.142 mmol) and sodium bicarbonate (14.9 mg, 0.177 mmol) were combined in 1 mL of DMSO. The solution was degassed with argon and then heated in a microwave at 120° C. for 1 hr. The resulting mixture was extracted with ethyl acetate and ammonium chloride solution. The organic layer was concentrated and purified by 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. This material was triturated with ether in hexanes and filtered to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-phenyl]-3-[4-(morpholine-4-carbonyl)-phenylamino]-1H-pyrazole-4-carbonitrile (18.2 mg, 41.5% yield) as a pale pink solid. LC/MS clacd for C33H30FN7O3 (m/e) 591.24, obsd 592.0 (M+H, ES+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (s, 9H), 3.50 (br., 4H), 3.59 (br., 4H), 7.37 (d, J=8.6 Hz, 2H), 7.59 (d, J=8.3 Hz, 1H), 7.65-7.71 (m, 3H), 7.78 (d, J=13.1 Hz, 1H), 7.87-7.93 (m, 2H), 8.08 (s, 1H), 8.58 (d, J=2.3 Hz, 1H), 9.29 (s, 1H), 9.47 (s, 1H).

Workup

  1. customThe solution was degassed with argon
  2. extractionThe resulting mixture was extracted with ethyl acetate and ammonium chloride solution
  3. concentrationThe organic layer was concentrated
  4. custompurified by flash column chromatography
  5. customethyl acetate (containing 5% methanol) in hexanes (5% to 80% linear gradient in 15 minutes, 12 g silica gel)

Sources & evidence

ORD record
ord-6399ca580d5447c19aaf8ba7b84d7225
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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