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

HRID 563179Notes

Reaction equation

HRID 563179 reaction equation
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([NH:10][C@H:11]([C@@H:24]([OH:26])[CH3:25])[C:12]([NH:14][NH:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([NH:10][C@@H:11]([C:12]2[O:23][C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:15][N:14]=2)[C@@H:24]([OH:26])[CH3:25])[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-amineHCID 67006523N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide2×

Product 1

HCID 442006592-chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrileYield 25.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The crude material from the reaction above N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)benzohydrazide (intermediate 1b) (20.46 g, 52.89 mmol) was added to THF (800 mL) stirred at room temperature. Polystyrene fixed (2-tert-butylamino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazophosphorine) PS-BEMP (72.12 g, 158.67 mmol base, 2.2 mmol loading per gram base, Aldrich Chemical Company) was added to the solution followed by slow addition of para-toluenesulfonyl chloride (p-TSCl) (12.10 g, 63.47 mmol). The reaction mixture was stirred for 3 h and the progress of the reaction was monitored by TLC. After the completion of the reaction, the BEMP reagent was filtered off and the solution concentrated to get the crude material. The crude material was chromatographed on silica gel with hexanes:EtOAc (6:4) to get the product (5.0 g). 1H NMR (500 MHz, CDCl3, δ in ppm) 7.94 (d, J=9 Hz, 2H), 7.54 (m, 1H), 7.48 (m, 2H), 7.42 (d, J=9 Hz, 1H), 6.67 (d, J=9 Hz, 1H), 5.26 (d, J=9 Hz, 1H), 4.74 (d, J=9 Hz, 1H), 4.64 (m, 1H), 3.16 (d, J=5 Hz, 1H), 2.35 (s, 3H), 1.43 (d, J=6 Hz, 3H).

Workup

  1. additionwas added to the solution
  2. stirringThe reaction mixture was stirred for 3 h
  3. customAfter the completion of the reaction
  4. filtrationthe BEMP reagent was filtered off
  5. concentrationthe solution concentrated
  6. customto get the crude material
  7. customThe crude material was chromatographed on silica gel with hexanes:EtOAc (6:4)

Sources & evidence

ORD record
ord-ec4af6e909d14d72bd7ccc9fc67456aa
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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