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

HRID 892318Notes

Reaction equation

HRID 892318 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][N:9]=[C:10](Cl)[S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=[CH:6][CH:7]=1.[I:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][CH:26]=[C:25](N3CCOCC3)[C:24]2=[O:35])=[CH:19][CH:18]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:25]3[C:24](=[O:35])[N:23]([C:20]4[CH:21]=[CH:22][C:17]([I:16])=[CH:18][CH:19]=4)[CH2:28][CH2:27][C:26]=3[C:10]([S:11]([CH3:14])(=[O:13])=[O:12])=[N:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 222404531-(4-Iodophenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one2×HCID 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-7-a-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-c9e2c589e35545bc80d31851d3c6df43
Source dataset
uspto-grants-2006_02
Patent number
US07005435B2

Reaction notes

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