Water → (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide

HRID 546187ノート

反応式

HRID 546187 の反応式
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:35])[C@@H:16]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[C:26]([Cl:34])[CH:25]=2)[CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)=[N:10]1)(C)(C)C.O1CCCC1.O>C(O)(=O)C>[Cl:34][C:26]1[CH:25]=[C:24]([C@@H:16]([CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:35])[CH:29]=[CH:28][C:27]=1[S:30]([CH3:33])(=[O:32])=[O:31]

参加物

5

反応物 3

HCID 962WaterHCID 8028TetrahydrofuranHCID 67188652(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide

生成物 1

HCID 24889503(R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide収率 99%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
25 °C

実験手順

In a round bottom flask was placed (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide (85 mg, 0.15 mmol), tetrahydrofuran (2 mL), water (0.5 mL) and acetic acid (2 mL). This solution was then stirred at 25° C. until all starting material is consumed (˜4 hr). The reaction was then diluted with water (10 mL) and transferred to a separatory funnel where it was extracted with ethyl acetate (3×10 mL). The organic layers were combined and then washed with saturated aqueous sodium bicarbonate solution (10 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate) afforded (R)-2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-propionamide (67 mg, 99%) as a white foam: [α]29589=−11.5° (c=0.13, methylene chloride); ES-HRMS m/e calcd for C20H24N3O5SCl (M+H)+ 454.1198, observed 454.1193; 1H NMR (300 MHz, DMSO-d6) δ 1.51 (m, 1H, CH), 1.78-2.30 (m, 8H, 4×CH2), 3.34 (s, 3H, SO2CH3), 3.67 (q, J=5.4 Hz, 2H, OCH2), 3.96 (m, 1H, ArCHCO), 4.00 (m, 2H, NCH2), 4.84 (t, J=5.4 Hz, 1H, OH), 6.41 (d, J=2.1 Hz, 1H, Ar), 7.55 (d, J=2.1 Hz, 1H, Ar), 7.62 (d, Jo=8.3 Hz, 1H, Ar), 7.73 (s, 1H, Ar), 8.02 (d, Jo=8.3 Hz, 1H, Ar), 10.85 (s, 1H, NH).

後処理

  1. customIn a round bottom flask was placed
  2. customis consumed (˜4 hr)
  3. additionThe reaction was then diluted with water (10 mL)
  4. customtransferred to a separatory funnel
  5. extractionwhere it was extracted with ethyl acetate (3×10 mL)
  6. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification on an AnaLogix Intelliflash system (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate)

出典と根拠

ORDレコード
ord-b52f1507b9df417db038dcc34158a91d
出典データセット
uspto-grants-2011_05
特許番号
US07935699B2

反応ノート

読み込み中…