Triethylamine → 1-(3-Chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one

HRID 890538Notes

Reaction equation

HRID 890538 reaction equation
ClC1C=C(NN=C(Cl)S(C)(=O)=O)C=CC=1.IC1C=CC(N2CCC=C(N3CCOCC3)C2=O)=CC=1.C(N(CC)CC)C.[Cl:43][C:44]1[CH:45]=[C:46]([N:50]2[C:54]3(N4CCOCC4)[C:55](=[O:66])[N:56]([C:59]4[CH:64]=[CH:63][C:62]([I:65])=[CH:61][CH:60]=4)[CH2:57][CH2:58][CH:53]3[C:52]([S:73]([CH3:76])(=[O:75])=[O:74])=[N:51]2)[CH:47]=[CH:48][CH:49]=1>C1(C)C=CC=CC=1>[Cl:43][C:44]1[CH:45]=[C:46]([N:50]2[C:54]3[C:55](=[O:66])[N:56]([C:59]4[CH:60]=[CH:61][C:62]([I:65])=[CH:63][CH:64]=4)[CH2:57][CH2:58][C:53]=3[C:52]([S:73]([CH3:76])(=[O:75])=[O:74])=[N:51]2)[CH:47]=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 222404531-(4-Iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one2×HCID 222500951-(3-Chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-7a-morpholin-4-yl-1,3a,4,5,6,7a-hexahydro-pyrazolo[3,4-c]pyridin-7-oneHCID 73877352N-(3-chlorophenyl)-1-(methylsulfonyl)-methanehydrazonoyl chloride

Product 1

HCID 222404561-(3-Chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-oneYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

The methanehydrazonoyl chloride (8.47 g, 31.7 mmol) and 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (12.17 g, 31.7 mmol) were combined in anhydrous toluene. The solution heated to 70° C. and triethylamine (13.2 mL, 95.1 mmol) was added dropwise. After the addition was complete the reaction was warmed to 90° C. and stirred at this temperature for 14 h. Analysis by LC/MS indicated formation of 1-(3-chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-7a-morpholin-4-yl-1,3a,4,5,6,7a-hexahydro-pyrazolo[3,4-c]pyridin-7-one complete with less than 5% of 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one remaining. The solvent was removed in vacuo. To the viscous oil was added dichloromethane (50 mL) then trifluoroacetic acid (30 mL) and heated to reflux for 4 h. The solvent was evaporated and the residue purified by flash column chromatography eluting with a gradient of hexane to 40% ethylacetate/hexane to give 10.65 g (64%) of 1-(3-chloro-phenyl)-6-(4-iodo-phenyl)-3-methanesulfonyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one.

Workup

  1. additionAfter the addition
  2. temperaturewas warmed to 90° C.
  3. customThe solvent was removed in vacuo
  4. additionTo the viscous oil was added dichloromethane (50 mL)
  5. temperaturetrifluoroacetic acid (30 mL) and heated
  6. temperatureto reflux for 4 h
  7. customThe solvent was evaporated
  8. customthe residue purified by flash column chromatography
  9. washeluting with a gradient of hexane to 40% ethylacetate/hexane

Sources & evidence

ORD record
ord-5df2db8351a947c286fc3b55251d6b65
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

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