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 2056698ノート

反応式

HRID 2056698 の反応式
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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 80711,2-Dimethoxyethane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-eac4814e4de64beb9c52c405f622da73
出典データセット
uspto-grants-2008_02
特許番号
US07335672B2

反応ノート

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