Cyanomethylenetributylphosphorane → HCID 178503317, compound

HRID 1269928Notes

Reaction equation

HRID 1269928 reaction equation
[CH3:1][S:2][C:3]1[C:11]([OH:12])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2.O[C@H:14]1[CH2:19][CH2:18][C@H:17]([N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])[CH2:16][CH2:15]1.CS(C1C(OC2CCCN(C(OC(C)(C)C)=O)CC2)=CC=C2C=1C=NN2)(=O)=O.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH3:1][S:2][C:3]1[C:11]([O:12][C@@H:14]2[CH2:15][CH2:16][C@H:17]([N:20]3[C:21](=[O:30])[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:28]3=[O:29])[CH2:18][CH2:19]2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2

Participants

6

Reactant 4

HCID 4622928CyanomethylenetributylphosphoraneHCID 229336484-(methylthio)-1H-indazol-5-olHCID 22933794HCID 22933794, compoundHCID 178515017HCID 178515017, compound

Product 1

HCID 178503317HCID 178503317, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The 4-(methylthio)-1H-indazol-5-ol (0.166 g, 0.92 mmol) obtained in Example 607 and the trans-2-(4-hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione (0.151 g, 0.61 mmol) obtained in Example 323, (a) were added to a solution of cyanomethylenetri-n-butylphosphorane (0.247 g, 0.92 mmol) in toluene (6 ml), and the resulting mixture was heated at 100° C. and stirred for 7 hours. The reaction solution was concentrated and then diluted with chloroform, and a 1N-aqueous sodium hydroxide solution was added thereto, followed by extraction with chloroform (three times). The extract solution was dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1˜1/1) to obtain 2-(cis-4-{[4-(methylthio)-1H-indazol-5-yl]oxy}cyclohexyl)-1H-isoindole-1,3(2H)-dione (0.144 g: 58%).

Workup

  1. concentrationThe reaction solution was concentrated
  2. additiondiluted with chloroform
  3. additiona 1N-aqueous sodium hydroxide solution was added
  4. extractionfollowed by extraction with chloroform (three times)
  5. dry with materialThe extract solution was dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off
  7. customthe residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1˜1/1)

Sources & evidence

ORD record
ord-45618f7a7ec74444834daa30315ddd74
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

Loading…