Triethylamine → N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(1H-pyrazol-1-yl)benzohydrazide

HRID 563290Notes

Reaction equation

HRID 563290 reaction equation
[Cl:1][C:2]1[C:3]([CH3:18])=[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].[N:19]1([C:24]2[CH:33]=[CH:32][C:27]([C:28]([NH:30][NH2:31])=[O:29])=[CH:26][CH:25]=2)[CH:23]=[CH:22][CH:21]=[N:20]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([NH:31][NH:30][C:28](=[O:29])[C:27]2[CH:26]=[CH:25][C:24]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:33][CH:32]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 432366724-(1H-Pyrazol-1-yl)benzohydrazideHCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine

Product 1

HCID 67005755N'-((2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoyl)-4-(1H-pyrazol-1-yl)benzohydrazide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a pre-cooled (−45° C.) solution of (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (134 mg, 0.50 mmol) and 4-(1H-pyrazol-1-yl)benzohydrazide (101 mg, 0.50 mmol) in anhydrous THF (10 mL) was added 1-Hydroxybenzotriazole monohydrate (77 mg, 0.50 mmol) and N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide-HCl (192 mg, 1.00 mmol) at −45° C. followed by triethylamine (0.14 mL, 1.00 mmol). The reaction mixture warmed to room temperature and stirred for 48 h, then quenched with 5% aq. citric acid (30 mL). The solution was extracted with EtOAc (30 mL). The organic extract was washed with 5% aq. Citric acid (2×20 mL), sat. aq. NaHCO3 (3×20 mL), H2O (2×20 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the title compound as an off white solid (164 mg, 73%): 1H NMR (400 MHz, CDCl3, δ in ppm) 8.85 (br s, 1H), 7.99 (d, J=2.5 Hz, 1H), 7.89 (d, J=8.6 Hz, 2H), 7.80-7.72 (m, 3H), 7.37 (dd, J=3.7, 8.2 Hz, 1H), 6.54-6.50 (m, 1H), 6.45 (dd, J=5.7, 8.6 Hz, 1H), 5.25 (d, J=6.3 Hz, 1H), 4.71 (br s, 1H), 4.53-4.45 (m, 1H), 2.32 (s, 3H), 1.36 (d, J=6.3 Hz, 3H).

Workup

  1. customquenched with 5% aq. citric acid (30 mL)
  2. extractionThe solution was extracted with EtOAc (30 mL)
  3. extractionThe organic extract
  4. washwas washed with 5% aq. Citric acid (2×20 mL), sat. aq. NaHCO3 (3×20 mL), H2O (2×20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-26ab30dc240a4a5c8061098d5a79395a
Source dataset
uspto-grants-2011_11
Patent number
US08067448B2

Reaction notes

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