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 2388425Notes

Reaction equation

HRID 2388425 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-f6b1de5ef81648629b4cf28dff9a1bbe
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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