Dimethyl Sulfoxide → Flt-3 Inhibitor III

HRID 1713630Notes

Reaction equation

HRID 1713630 reaction equation
[Si](Br)(C)(C)C.CS(C)=O.[C:10]1([CH2:16][CH:17]=O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[N:19]1([CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH2:36])=[S:35])=[CH:29][CH:28]=2)[CH2:23][CH2:22][CH2:21][CH2:20]1>CC#N>[C:10]1([C:16]2[S:35][C:34]([NH:33][C:30]3[CH:31]=[CH:32][C:27]([O:26][CH2:25][CH2:24][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[CH:28][CH:29]=3)=[N:36][CH:17]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 998PhenylacetaldehydeHCID 76113BromotrimethylsilaneHCID 11846123[4-(2-Pyrrolidin-1-ylethoxy)phenyl]thiourea

Product 1

HCID 11772958Flt-3 Inhibitor III

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Me3SiBr (0.052 mL, 0.384 mmol, 1.1 equiv) and DMSO (0.027 mL, 0.384 mmol, 1.1 equiv) are added sequentially and dropwise to a cold (0° C.) solution of phenylacetaldehyde (42 mg, 0.349 mmol) in CH3CN (0.66 mL), under an argon atmosphere. The resulting mixture is stirred at 0° C. for 50 min, allowed to warm to RT and to stir for 10 min. CH3CN (0.97 mL) is added to the reaction mixture, followed by addition of [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-thiourea (93 mg, 0.349 mmol). The reaction mixture is heated to reflux for 80 min, allowed to cool to RT and concentrated in vacuo. Purification of the crude product by silica gel (20 g) column chromatography (CH2Cl2/MeOH, 90/10) affords the title compound: ES-MS: 366.0 [M+H]+; single peak at tR=6.33 min (System 1); Rf=0.11 (CH2Cl2/MeOH, 80/20).

Workup

  1. temperatureto warm to RT
  2. stirringto stir for 10 min
  3. temperatureThe reaction mixture is heated
  4. temperatureto reflux for 80 min
  5. temperatureto cool to RT
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude product by silica gel (20 g) column chromatography (CH2Cl2/MeOH, 90/10)

Sources & evidence

ORD record
ord-e3e36f1bc3e54fee83216959eba5d7d7
Source dataset
uspto-grants-2010_09
Patent number
US07795288B2

Reaction notes

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