4-Toluenesulfonyl chloride → 2-chloro-4-((1R,2R)-2-hydroxy-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile

HRID 2388425ノート

反応式

HRID 2388425 の反応式
[Cl:1][C:2]1[C:3]([CH3:31])=[C:4]([NH:10][C@H:11]([C@H:28]([OH:30])[CH3:29])[C:12]([NH:14][NH:15][C:16](=O)[C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].S(Cl)(C1C=CC(C)=CC=1)(=O)=O.C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:31])=[C:4]([NH:10][C@@H:11]([C:12]2[O:13][C:16]([C:17]3[CH:18]=[CH:19][C:20]([S:23]([CH3:26])(=[O:24])=[O:25])=[CH:21][CH:22]=3)=[N:15][N:14]=2)[C@H:28]([OH:30])[CH3:29])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

参加物

5

反応物 3

HCID 73974-Toluenesulfonyl chlorideHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amine2 回HCID 67005955N'-((2R,3R)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)-4-(methylsulphonyl)benzohydrazide

生成物 1

HCID 442009982-chloro-4-((1R,2R)-2-hydroxy-1-(5-(4-(methylsulfonyl)phenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile収率 26%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a 250 mL, round-bottomed flask equipped with a magnetic stir bar and septum was added N′-((2R,3R)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)-4-(methylsulphonyl)benzohydrazide (855 mg, 1.8 mmol) followed by a addition of anhydrous THF (200 mL) under an atmosphere of nitrogen. To this was then added tosyl chloride (350 mg, 1.8 mmol) followed by addition of polystyrene bound (2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (PS-BEMP) (2.2 mmol/g loading, 2.51 g, 5.5 mmol). This mixture was allowed to stir at room temperature for 6.5 h. The solids were then filtered off and washed with additional THF (100 mL). The filtrate was then concentrated under reduced pressure to reveal a red solid. This was purified via silica gel chromatography eluted with 70% EtOAc/hexanes to yield product as a white solid (209 mg, 25%). 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.25 (AA′XX′, J=8.4 Hz, 2H), 8.13 (AA′XX′, J=8.8 Hz, 2H), 7.49 (d, J=8.8 Hz, 1H), 6.90 (d, J=8.8 Hz, 1H), 5.90 (d, J=9.0 Hz, 1H), 5.11 (dd, J=5.6, 8.9 Hz, 1H), 4.70 (d, J=6.0 Hz, 1H), 4.55 (m, 1H), 3.19 (s, 3H), 2.37 (s, 3H), 1.43 (d, J=6.2 Hz, 3H).

後処理

  1. customTo a 250 mL, round-bottomed flask equipped with a magnetic stir bar
  2. filtrationThe solids were then filtered off
  3. washwashed with additional THF (100 mL)
  4. concentrationThe filtrate was then concentrated under reduced pressure
  5. customThis was purified via silica gel chromatography
  6. washeluted with 70% EtOAc/hexanes

出典と根拠

ORDレコード
ord-f6b1de5ef81648629b4cf28dff9a1bbe
出典データセット
uspto-grants-2012_09
特許番号
US08268872B2

反応ノート

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