3,4-dichloro-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)benzohydrazide → 2-Chloro-4-((1R,2S)-1-(5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-methylbenzonitrile

HRID 563296Notes

Reaction equation

HRID 563296 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[C:5]([NH:7][NH:8][C:9](=[O:25])[C@H:10]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[C:17]([Cl:23])[C:16]=1[CH3:24])[C@@H:11]([OH:13])[CH3:12])=O.C(NP1(N(CC)CC)N(C)CCCN1C)(C)(C)C>C1COCC1>[Cl:23][C:17]1[C:16]([CH3:24])=[C:15]([NH:14][C@@H:10]([C:9]2[O:25][C:5]([C:4]3[CH:26]=[CH:27][C:28]([Cl:29])=[C:2]([Cl:1])[CH:3]=3)=[N:7][N:8]=2)[C@@H:11]([OH:13])[CH3:12])[CH:20]=[CH:19][C:18]=1[C:21]#[N:22]

Participants

4

Reactant 2

HCID 670064343,4-dichloro-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)benzohydrazideHCID 178464497HCID 178464497, compound

Product 1

HCID 441997082-Chloro-4-((1R,2S)-1-(5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-methylbenzonitrileYield 25.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,4-dichloro-N′-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)benzohydrazide (1.35 g, 2.9 mmol) in anhydrous THF (100 mL) at room temperature was added 2-tert-butylamino-2-diethylamino-1,3-dimethyl perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol base/g) (4.0 g) followed by p-TSCl (621 mg, 3.2 mmol) and the mixture was stirred for 1 h. The mixture was filtered under suction and the residue washed with acetone (50 mL) followed by MeOH (50 mL). The filtrate was then concentrated and subjected to flash column chromatography [EtOAc-Hexanes (1:12)] to give the desired product (324 mg, 25%). 1H NMR (500 MHz, acetone-d6, δ in ppm) 8.07 (d, J=2.1 Hz, 1H), 7.81 (dd, J=2.1 Hz, 8.3 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 6.65 (d, J=8.6 Hz, 1H), 5.22 (d, J=8.3 Hz, 1H), 4.75 (dd, J=2.8 Hz, 8.2 Hz, 1H), 4.66-4.59 (m, 1H), 2.77 (d, J=3.6 Hz, 1H), 2.35 (s, 3H), 1.43 (d, J=6.3 Hz, 3H).

Workup

  1. filtrationThe mixture was filtered under suction
  2. washthe residue washed with acetone (50 mL)
  3. concentrationThe filtrate was then concentrated

Sources & evidence

ORD record
ord-9bd564c2b4f64dc29db5bc310deabefc
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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