Sodium hydride → tert-Butyl 4-(6-bromothiazolo[4,5-b]pyridin-2-yloxy)piperidine-1-carboxylate

HRID 1429537ノート

反応式

HRID 1429537 の反応式
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Cl.[Br:18][C:19]1[CH:20]=[C:21]2[S:27][C:26](Cl)=[N:25][C:22]2=[N:23][CH:24]=1.[Na]>CN(C=O)C>[Br:18][C:19]1[CH:20]=[C:21]2[S:27][C:26]([O:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)=[N:25][C:22]2=[N:23][CH:24]=1

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5360545SodiumHCID 674627556-Bromo-2-chlorothiazolo[4,5-b]pyridine hydrochloride

生成物 1

HCID 68208481tert-Butyl 4-(6-bromothiazolo[4,5-b]pyridin-2-yloxy)piperidine-1-carboxylate収率 21%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (0.88 g, 4.37 mmol) in DMF (8.7 mL) was added NaH (0.121 g, 4.81 mmol) at 0° C. Upon completion of addition, the mixture was warmed to rt until the mixture became a clear solution. In a separate flask, 6-bromo-2-chlorothiazolo[4,5-b]pyridine hydrochloride (0.5 g, 1.748 mmol) was suspended in DMF (8.74 mL) and the above sodium salt solution was transferred into the thiazolepyridine suspension via cannulation. The resulting mixture was then heated in a 50° C. oil bath. After 4 h, the reaction mixture was analyzed by HPLC, which indicated the reaction was complete. The reaction mixture was cooled to rt, and then quenched with NaHCO3 (saturated aq, 10 mL). The resulting mixture was extracted with EtOAc (3×5 mL) and the combined organic layers were dried (Na2SO4), filtered, and concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to give Compound 21B as a white solid (150 mg, 21% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 8.54 (d, J=2.2 Hz, 1H), 8.08 (d, J=2.2 Hz, 1H), 5.43-5.52 (m, J=8.0, 8.0, 4.0, 3.9 Hz, 1H), 3.70-3.84 (m, 2H), 3.24-3.34 (m, 2H), 2.07-2.17 (m, 2H), 1.80-1.92 (m, J=12.7, 8.5, 8.5, 4.1 Hz, 2H), 1.46 (s, 9H). LC/MS (m/z)=415 (M+H)+.

後処理

  1. additionUpon completion of addition
  2. temperatureThe resulting mixture was then heated in a 50° C. oil bath
  3. temperatureThe reaction mixture was cooled to rt
  4. customquenched with NaHCO3 (saturated aq, 10 mL)
  5. extractionThe resulting mixture was extracted with EtOAc (3×5 mL)
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield the crude product
  10. customThe crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc)

出典と根拠

ORDレコード
ord-59aed915244e42648205d1dc11d5a118
出典データセット
uspto-grants-2015_01
特許番号
US08940716B2

反応ノート

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