Potassium Carbonate → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(R),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamide

HRID 720011ノート

反応式

HRID 720011 の反応式
[C:1](=[O:4])([O-])[O-].[K+].[K+].[CH2:7]([C:10]1[N:11]=[CH:12][C:13]([NH:16][C:17](=[O:36])[C@@H:18]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[C:27]([Cl:35])[CH:26]=2)[CH2:19][CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)=[N:14][CH:15]=1)C=C.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].[C:46]([OH:50])(C)(C)C.O>C(OCC)(=O)C.[Cl-].[Na+].O.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[Os](=O)(=O)(=O)=O.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.C1(C)C=CC=CC=1>[Cl:35][C:27]1[CH:26]=[C:25]([C@@H:18]([CH2:19][CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[C:17]([NH:16][C:13]2[CH:12]=[N:11][C:10]([CH2:7][C@@H:1]([OH:4])[CH2:46][OH:50])=[CH:15][N:14]=2)=[O:36])[CH:30]=[CH:29][C:28]=1[S:31]([CH3:34])(=[O:33])=[O:32]

参加物

12

反応物 4

HCID 11430Potassium CarbonateHCID 656671Sodium PyrosulfiteHCID 67482647N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamideHCID 714019492-Methylpropan-2-ol--water (1/1)

生成物 1

HCID 117549672(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(R),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamide収率 89%

試薬・触媒・溶媒 7

HCID 1140Toluene触媒HCID 30318Osmium Tetroxide触媒HCID 112172021,4-Bis(dihydroquinidine)phthalazine触媒HCID 178511488HCID 178511488、化合物触媒HCID 962Water溶媒HCID 5234Sodium Chloride溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A yellow solution of potassium ferricyanide (1.00 g, 3.037 mmol), potassium carbonate (430.0 mg, 3.111 mmol), and (DHQD)2PHAL (19.0 mg, 0.0244 mmol) in tert-butyl alcohol/water (16.0 mL, 1:1) was cooled to 0° C. and then treated with a 0.2M solution of osmium tetroxide in toluene (0.048 mL, 0.0096 mmol) followed by N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide (prepared as in Example 81, 446.0 mg, 0.996 mmol). The reaction mixture was stirred at 0° C. for 4 h. The reaction mixture was then diluted with ethyl acetate and sodium metabisulfite (0.45 g, 2.37 mmol) and allowed to warm to 25° C. where it was stirred for 15 min. The mixture was diluted with a saturated aqueous sodium chloride solution and water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/3 hexanes/ethyl acetate to ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(R),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamide (469.2 mg, 89%) as a white foam: mp 64–69° C. (foam to gel); (ES)+-HRMS m/e calcd for C22H28ClN3O5S (M+H)+ 482.1511, found 482.1511.

後処理

  1. temperatureto warm to 25° C. where it
  2. stirringwas stirred for 15 min
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-54df15c9d69e40c1a8388804404b6a23
出典データセット
uspto-grants-2006_11
特許番号
US07132425B2

反応ノート

読み込み中…