Sodium Carbonate → N-(4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

HRID 2056698Notes

Reaction equation

HRID 2056698 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][C:9]2[C:14]3[N:15]=[C:16]([NH:18][C:19](=[O:21])[CH3:20])[S:17][C:13]=3[CH:12]=[CH:11][CH:10]=2)[CH:5]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:40]2[CH2:45][CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][CH:41]=2)O1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C([O-])(O)=O.[Na+].CC([O-])=O.CC([O-])=O.[Pd+2]>[NH:43]1[CH2:42][CH:41]=[C:40]([C:2]2[N:7]=[C:6]([O:8][C:9]3[C:14]4[N:15]=[C:16]([NH:18][C:19](=[O:21])[CH3:20])[S:17][C:13]=4[CH:12]=[CH:11][CH:10]=3)[CH:5]=[C:4]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)[N:3]=2)[CH2:45][CH2:44]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 58612070N-{4-[2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzo[d]thiazol-2-yl}-acetamide

Product 1

HCID 11598707N-(4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-{4-[2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide (300 mg, 0.645 mmol, Example 7(d)), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (216 mg, 0.70 mmol, Aldrich), Pd(OAc)2 (7.2 mg, 0.03 mmol, Aldrich), PPh3 (17 mg, 0.065 mmol) and 2N aqueous Na2CO3 (0.65 mL) in 1,2-dimethoxyethane (3.0 mL) was heated at 120° C. in a microwave synthesizer for 25 min. The reaction mixture was cooled to room temperature, diluted with saturated aqueous solution of NaHCO3 (10 mL) and extracted with EtOAc (2×50) mL. The combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The yellow solid residue was dissolved in DCM (4 mL) and treated with trifluoroacetic acid (1 mL). The mixture was stirred at room temperature for 1.5 h and the volatiles were evaporated in vacuo. The residue was partitioned between 1N HCl (5 mL) and Et2O (5 mL). The aqueous layer was separated, basified with 2N NaOH, and extracted with EtOAc (3×15 mL). The combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue by silica gel column chromatography (gradient 1-25% (2N NH3 in MeOH)/EtOAc) afforded the title compound as an off-white solid. MS (ESI, pos. ion.) m/z: 512 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×50) mL
  3. dry with materialThe combined EtOAc extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe yellow solid residue was dissolved in DCM (4 mL)
  7. additiontreated with trifluoroacetic acid (1 mL)
  8. customthe volatiles were evaporated in vacuo
  9. customThe residue was partitioned between 1N HCl (5 mL) and Et2O (5 mL)
  10. customThe aqueous layer was separated
  11. extractionextracted with EtOAc (3×15 mL)
  12. dry with materialThe combined EtOAc extracts were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customPurification of the residue by silica gel column chromatography (gradient 1-25% (2N NH3 in MeOH)/EtOAc)

Sources & evidence

ORD record
ord-eac4814e4de64beb9c52c405f622da73
Source dataset
uspto-grants-2008_02
Patent number
US07335672B2

Reaction notes

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