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

HRID 1064059Notes

Reaction equation

HRID 1064059 reaction equation
C(Cl)=NN.IC1C=CC(N2CCC=C(N3CCOCC3)C2=O)=CC=1.C(N(CC)CC)C.[Cl:32][C:33]1[CH:34]=[C:35]([N:39]2[C:43]3(N4CCOCC4)[C:44](=[O:55])[N:45]([C:48]4[CH:53]=[CH:52][C:51]([I:54])=[CH:50][CH:49]=4)[CH2:46][CH2:47][CH:42]3[C:41]([S:62]([CH3:65])(=[O:64])=[O:63])=[N:40]2)[CH:36]=[CH:37][CH:38]=1>C1(C)C=CC=CC=1>[Cl:32][C:33]1[CH:34]=[C:35]([N:39]2[C:43]3[C:44](=[O:55])[N:45]([C:48]4[CH:49]=[CH:50][C:51]([I:54])=[CH:52][CH:53]=4)[CH2:46][CH2:47][C:42]=3[C:41]([S:62]([CH3:65])(=[O:64])=[O:63])=[N:40]2)[CH:36]=[CH:37][CH:38]=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 85832306Methanehydrazonoyl 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-bc0a94cfeea24227bd7a25919fb7f1f2
Source dataset
uspto-grants-2005_11
Patent number
US06967208B2

Reaction notes

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