Sodium hydride → 6-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole

HRID 1429524ノート

反応式

HRID 1429524 の反応式
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].[H-].[Na+].[Br:19][C:20]1[CH:29]=[CH:28][C:23]2[N:24]=[C:25](Cl)[S:26][C:22]=2[CH:21]=1>CN(C=O)C.O>[Br:19][C:20]1[CH:29]=[CH:28][C:23]2[N:24]=[C:25]([O:16][CH:13]3[CH2:14][CH2:15][N:10]([C:7]4[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=4)[CH2:11][CH2:12]3)[S:26][C:22]=2[CH:21]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 20498716-Bromo-2-chlorobenzothiazoleHCID 670724781-(5-Propylpyrimidin-2-yl)piperidin-4-ol

生成物 1

HCID 674627936-Bromo-2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazole収率 74.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol (160 mg, 0.724 mmol) in DMF (5 mL) was added NaH (36.2 mg, 0.905 mmol) at 0° C. Upon completion of addition, the reaction mixture was allowed to warm to rt and then 6-bromo-2-chlorobenzo[d]thiazole (150 mg, 0.604 mmol) was added. The resulting mixture was heated to 90° C., where it stirred overnight. At the conclusion of this period, the reaction mixture was cooled to rt, diluted with water and then extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4. The resulting mixture was filtered and concentrated under reduced pressure to yield the crude product. The crude product was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 50% EtOAc) to afford Compound 1C (194 mg, 0.448 mmol, 74.2% yield).

後処理

  1. additionUpon completion of addition
  2. temperatureThe resulting mixture was heated to 90° C.
  3. temperatureAt the conclusion of this period, the reaction mixture was cooled to rt
  4. extractionextracted with EtOAc (3×5 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationThe resulting mixture was filtered
  7. concentrationconcentrated under reduced pressure
  8. customto yield the crude product
  9. 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-f6183abc30f7493fab695737dbc873e3
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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