Sodium Carbonate → N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)-2-chlorobenzamide

HRID 390430

Reaction equation

HRID 390430 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[N:19]=[C:18]([Cl:20])[CH:17]=[C:16](Cl)[N:15]=2)=[CH:9][CH:8]=1)=[O:5].[S:26]1[C:30]([NH2:31])=[N:29][CH:28]=[N:27]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[S:26]1[C:30]([NH:31][C:16]2[CH:17]=[C:18]([Cl:20])[N:19]=[C:14]([S:13][C:10]3[CH:11]=[CH:12][C:7]([NH:6][C:4](=[O:5])[C:3]4[CH:22]=[CH:23][CH:24]=[CH:25][C:2]=4[Cl:1])=[CH:8][CH:9]=3)[N:15]=2)=[N:29][CH:28]=[N:27]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2902745-Amino-1,2,4-thiadiazoleHCID 594207972-Chloro-N-(4-(4,6-dichloropyrimidin-2-ylthio)phenyl)benzamide

Product 1

HCID 86644548N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)-2-chlorobenzamideYield 109.5%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

2-Chloro-N-(4-(4,6-dichloropyrimidin-2-ylthio)phenyl)benzamide (300 mg, 0.73 mmol), 1,2,4-thiadiazole-5-amine (74 mg, 0.73 mmol), Pd2 dba3 (36 mg), xantphos (46 mg), sodium carbonate (128 mg, 1.21 mmol) in 1,4-dioxane (10 mL) were flushed for 15 minutes with nitrogen and then heated in the microwave to 130° C. for 2 hours. The crude reaction mixture was poured in methanol, filtered through Celite and concentrated. Ethyl acetate and saturated aqueous sodium bicarbonate were added and the organic layer was dried over sodium sulfate, filtered, and concentrated to dryness to yield 380 mg N-(4-(4-(1,2,4-thiadiazol-5-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)-2-chlorobenzamide with 50-60% purity (HPLC method A, Rf=8.576 minutes) that was used as such in the next step.

Workup

  1. customThe crude reaction mixture
  2. filtrationfiltered through Celite
  3. concentrationconcentrated
  4. additionEthyl acetate and saturated aqueous sodium bicarbonate were added
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-63e53733565f43d3acf3b034b28bcf84
Source dataset
uspto-grants-2013_02
Patent number
US08383633B2

Linked notes

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