4-Cyano-N'-((2R,3R)-2-(4-cyanonaphthalen-1-ylamino)-3-hydroxybutanoyl)benzohydrazide → 4-((1R,2R)-1-(5-(4-Cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-1-naphthonitrile

HRID 563285Notes

Reaction equation

HRID 563285 reaction equation
[C:1]([C:3]1[CH:31]=[CH:30][C:6]([C:7]([NH:9][NH:10][C:11](=O)[C@H:12]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([C:27]#[N:28])=[CH:19][CH:18]=2)[C@H:13]([OH:15])[CH3:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].C(NP1(N(CC)CC)N(C)CCCN1C)(C)(C)C>C1COCC1>[C:1]([C:3]1[CH:31]=[CH:30][C:6]([C:7]2[O:8][C:11]([C@H:12]([NH:16][C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]([C:27]#[N:28])=[CH:19][CH:18]=3)[C@H:13]([OH:15])[CH3:14])=[N:10][N:9]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 670059464-Cyano-N'-((2R,3R)-2-(4-cyanonaphthalen-1-ylamino)-3-hydroxybutanoyl)benzohydrazideHCID 178464497HCID 178464497, compound

Product 1

HCID 670064834-((1R,2R)-1-(5-(4-Cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-1-naphthonitrileYield 3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-cyano-N′-((2R,3R)-2-(4-cyanonaphthalen-1-ylamino)-3-hydroxybutanoyl)benzohydrazide (900 mg, 2.18 mmol) in anhydrous THF (90 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) (2.97 g, 6.53 mmol) followed by p-TSCl (498 mg, 2.60 mmol) and the mixture was stirred for 75 minutes. The mixture was filtered and the residue washed with acetone (3×100 mL) followed by MeOH (3×150 mL). The filtrate was concentrated under reduced pressure to provide an off white solid, which was purified by flash chromatography over silica gel (30-50% EtOAc in hexanes) to provided the title compound as a brown oil (25 mg, 3%): 1H NMR (400 MHz, CDCl3, δ in ppm) 8.19 (d, J=8.4 Hz, 2H), 8.18 (d, J=8.4 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.84 (d, J=8.6 Hz, 2H), 7.77 (d, J=8.2 Hz, 1H), 7.68 (t, J=7.4 Hz, 1H), 7.59 (t, J=7.2 Hz, 1H), 6.67 (d, J=8.2 Hz, 1H), 5.69 (d, J=9.6 Hz, 1H), 5.47 (d, J=3.7 Hz, 1H), 4.71 (dqd, J=3.7, 6.5, 9.9 Hz, 1H), 1.65 (d, J=6.4 Hz, 3H).

Workup

  1. filtrationThe mixture was filtered
  2. washthe residue washed with acetone (3×100 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto provide an off white solid, which
  5. customwas purified by flash chromatography over silica gel (30-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-adb75505b6034a0ba61f0ac9f8c07458
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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