Triethylamine → N'-((2R,3R)-2-(3-Chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

HRID 563269Notes

Reaction equation

HRID 563269 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([C@H:15]([OH:17])[CH3:16])[C:12]([OH:14])=O)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[C:18]([C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH2:27])=[O:25])=[CH:22][CH:21]=1)#[N:19].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([C@H:15]([OH:17])[CH3:16])[C:12]([NH:27][NH:26][C:24](=[O:25])[C:23]2[CH:22]=[CH:21][C:20]([C:18]#[N:19])=[CH:29][CH:28]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 4567324-CyanobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67006815(2R,3R)-2-(3-Chloro-4-cyanophenylamino)-3-hydroxybutanoic acid

Product 1

HCID 67006229N'-((2R,3R)-2-(3-Chloro-4-cyanophenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a pre-cooled (−30° C.) solution of (2R,3R)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoic acid (1.06 g, 4.16 mmol) and 4-cyanobenzohydrazide (671 mg, 4.16 mmol) in anhydrous THF (60 mL) was added 1-Hydroxybenzotriazole monohydrate (637 mg, 4.16 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide-HCl (1.60 g, 8.32 mmol) at −30° C. followed by triethylamine (1.16 mL, 8.32 mmol). The reaction mixture warmed to room temperature and stirred for 16 h, then quenched with 5% aq. citric acid (150 mL). The solution was extracted with EtOAc (150 mL). The organic extract was washed with 5% aq. citric acid (2×75 mL), sat. aq. NaHCO3 (3×80 mL), H2O (2×100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as an off white solid (1.65 g, 100%): 1H NMR (400 MHz, acetone-d6, δ in ppm) 8.11 (dm, J=8.8 Hz, 2H), 7.94 (dm, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 1H), 6.96 (d, J=2.3 Hz, 1H), 6.85 (dd, J=2.3, 8.8 Hz, 1H), 6.44 (d, J=7.4 Hz, 1H), 4.21-4.11 (m, 2H), 1.35 (d, J=6.3 Hz, 3H).

Workup

  1. customquenched with 5% aq. citric acid (150 mL)
  2. extractionThe solution was extracted with EtOAc (150 mL)
  3. extractionThe organic extract
  4. washwas washed with 5% aq. citric acid (2×75 mL), sat. aq. NaHCO3 (3×80 mL), H2O (2×100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-84f6447e5c604179b360eeb3a85681e7
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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