Potassium Carbonate → 6-[4-(5-{[4-Chloro-3-trifluoromethyl-phenyl]amino}-1,3,4-oxadiazol-2-yl)-phenoxy]-pyrimidine-2,4-diamine trifluoroacetic acid salt

HRID 387459Notes

Reaction equation

HRID 387459 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:13][C:12]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)=[N:11][N:10]=2)=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl[C:36]1[N:41]=[C:40]([NH2:42])[N:39]=[C:38]([NH2:43])[CH:37]=1.[C:44]([O-:47])([O-])=[O:45].[K+].[K+]>CN(C=O)C.CO>[F:22][C:21]([F:24])([F:23])[C:44]([OH:47])=[O:45].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:13][C:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:36]4[N:41]=[C:40]([NH2:42])[N:39]=[C:38]([NH2:43])[CH:37]=4)=[CH:18][CH:19]=3)=[N:11][N:10]=2)=[CH:4][C:3]=1[C:21]([F:22])([F:23])[F:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 674322,4-Diamino-6-chloropyrimidineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 1361796924-(5-{[4-Chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol

Product 1

HCID 866042856-[4-(5-{[4-Chloro-3-trifluoromethyl-phenyl]amino}-1,3,4-oxadiazol-2-yl)-phenoxy]-pyrimidine-2,4-diamine trifluoroacetic acid saltYield 93.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-(5-{[4-chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol (100 mg, 0.281 mmol) was dissolved in 2.5 mL of anhydrous DMF in a 5 mL microwave vial. Solid potassium bis(trimethylsilyl)amide (140.6 mg, 0.703 mmol) was added and the reaction mixture was stirred with heating at 80° C. for 15 min, then 6-chloro-2,4-diamino-pyrimidine (81.3 mg, 0.562 mmol) was added, followed by anhydrous K2CO3 (19.5 mg, 0.141 mmol). Then the vial was capped and microwaved at 200° C. for 15 min. Then the reaction mixture was diluted with ca. 1 mL of MeOH, filtered through 0.22 um syringe filter and purified by reverse-phase preparative HPLC in acetonitrile/water system with 0.01% TFA. The product was isolated as a TFA salt (75.8 mg of beige solid).

Workup

  1. customThen the vial was capped
  2. custommicrowaved at 200° C. for 15 min
  3. filtrationfiltered through 0.22 um syringe
  4. filtrationfilter
  5. custompurified by reverse-phase preparative HPLC in acetonitrile/water system with 0.01% TFA

Sources & evidence

ORD record
ord-c93daf4de0554cdba0760e71a18f249b
Source dataset
uspto-grants-2013_02
Patent number
US08372971B2

Reaction notes

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