Triethylamine → Methyl 4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoate

HRID 1429527ノート

反応式

HRID 1429527 の反応式
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([C:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH:31]=5)[CH:23]=[CH:22][C:20]=4[N:21]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].C(N(CC)CC)C.Cl[S:40]([CH2:43][CH2:44][CH2:45][C:46]([O:48][CH3:49])=[O:47])(=[O:42])=[O:41]>C(Cl)Cl>[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[S:18][C:19]4[CH:25]=[C:24]([C:26]5[CH2:27][CH2:28][N:29]([S:40]([CH2:43][CH2:44][CH2:45][C:46]([O:48][CH3:49])=[O:47])(=[O:42])=[O:41])[CH2:30][CH:31]=5)[CH:23]=[CH:22][C:20]=4[N:21]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 10608119Methyl 4-(chlorosulfonyl)butanoateHCID 674627952-(1-(5-Propylpyrimidin-2-yl)piperidin-4-yloxy)-6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazole

生成物 1

HCID 68208471Methyl 4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butanoate収率 68%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazole (60 mg, 0.138 mmol) and triethylamine (0.039 mL, 0.275 mmol) in CH2Cl2 (1.5 mL) at 0° C. was added methyl 4-(chlorosulfonyl)butanoate (41.5 mg, 0.207 mmol). Upon completion of addition, the reaction mixture was stirred at 0° C. for 15 min. At the conclusion of this period, the reaction mixture was allowed to warm to rt, where it stirred for 1 hr. After this time, the reaction mixture was quenched with saturated aq NaHCO3 (3 mL) and then extracted with CH2Cl2 (3×2 mL). The combined organic layers were washed with brine (2 mL), 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 afford Compound 5B (56 mg, 0.093 mmol, 68% yield). 1H NMR (500 MHz, chloroform-d) ppm 8.21 (2H, br. s.), 7.62-7.66 (2H, m), 7.37-7.42 (1H, m), 6.06-6.10 (1H, m), 5.43-5.51 (1H, m), 4.18-4.29 (2H, m), 4.00-4.06 (2H, m), 3.67-3.82 (4H, m), 3.60 (2H, t, J=5.6 Hz), 3.07-3.14 (2H, m), 2.65-2.72 (2H, m), 2.54 (2H, t, J=7.0 Hz), 2.43 (2H, t, J=7.6 Hz), 2.12-2.26 (4H, m), 1.92-2.05 (2H, m), 1.50-1.65 (3H, m), 0.96 (3H, t, J=7.3 Hz). LC/MS (m/z)=600 (M+H)+.

後処理

  1. additionUpon completion of addition
  2. temperatureto warm to rt
  3. stirringwhere it stirred for 1 hr
  4. customAfter this time, the reaction mixture was quenched with saturated aq NaHCO3 (3 mL)
  5. extractionextracted with CH2Cl2 (3×2 mL)
  6. washThe combined organic layers were washed with brine (2 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield the crude product
  11. 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-ce611972d38244a7afc8b156690e0dd2
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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