Potassium Carbonate → 2-Hydroxy-N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-propionamide

HRID 857643Notes

Reaction equation

HRID 857643 reaction equation
C([O:4][CH:5]([CH3:9])[C:6](O)=[O:7])(=O)C.[F:10][C:11]([F:36])([F:35])[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]3[C:30]4[N:31]=[C:32]([NH2:34])[S:33][C:29]=4[CH:28]=[CH:27][CH:26]=3)[CH:19]=2)=[CH:14][CH:13]=1.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C.CCN(P1(N(CC2C=CC=CC=2)CCCN1C)=NC(C)(C)C)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.C(=O)([O-])[O-].[K+].[K+]>S(Cl)(Cl)=O>[OH:4][CH:5]([CH3:9])[C:6]([NH:34][C:32]1[S:33][C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([O:24][C:20]3[CH:19]=[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:11]([F:35])([F:10])[F:36])=[CH:13][CH:14]=4)[N:23]=[CH:22][N:21]=3)[C:30]=2[N:31]=1)=[O:7]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 790412-Acetoxypropionic AcidHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 100916504-[6-(4-Trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-ylamineHCID 16216994BEMP resin

Product 1

HCID 104793572-Hydroxy-N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-propionamide

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (+/−)-2-acetoxypropionic acid (56 uL, 0.5 mmol, Fluka) in thionyl chloride (1 mL) was heated at reflux for 3 h. After evaporation of the solvent, the residue was dissolved in THF, and treated with 4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-ylamine, (Example 65), (97 mg, 0.25 mmol) and 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine, polymer bound (BEMP resin) (0.17 g, 0.38 mmol, Aldrich). The reaction mixture was stirred at 25° C. for 16 h. The insoluble material was filtered off and washed with CH2Cl2. The filtrate was concentrated and then dissolved in MeOH. Potassium carbonate (69 mg, 0.5 mmol) was added and the reaction mixture was stirred at 25° C. for 2 h. The solvent was evaporated in vacuum and to the residue was added CH2Cl2 (30 mL). After stirring for 5 min, the precipitate was collected by filtration and purified by silica gel chromatography (3:1 of EtOAc/hexanes) to give the title compound. MS (ESI, pos. ion) m/z: 461 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 h
  3. customAfter evaporation of the solvent
  4. dissolutionthe residue was dissolved in THF
  5. filtrationThe insoluble material was filtered off
  6. washwashed with CH2Cl2
  7. concentrationThe filtrate was concentrated
  8. dissolutiondissolved in MeOH
  9. stirringthe reaction mixture was stirred at 25° C. for 2 h
  10. customThe solvent was evaporated in vacuum and to the residue
  11. additionwas added CH2Cl2 (30 mL)
  12. stirringAfter stirring for 5 min
  13. filtrationthe precipitate was collected by filtration
  14. custompurified by silica gel chromatography (3:1 of EtOAc/hexanes)

Sources & evidence

ORD record
ord-4c22d78a83364e458d90e9f2aaa82754
Source dataset
uspto-grants-2006_12
Patent number
US07144888B2

Reaction notes

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