Triethylamine → HCID 67006171, compound

HRID 2388494Notes

Reaction equation

HRID 2388494 reaction equation
[Cl:1][C:2]1[C:3]([CH2:18][CH3:19])=[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:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([NH:28][NH2:29])=[O:27])=[CH:24][CH:23]=1)#[N:21].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]([CH2:18][CH3:19])=[C:4]([NH:10][C@H:11]([C@H:15]([OH:17])[CH3:16])[C:12]([NH:29][NH:28][C:26](=[O:27])[C:25]2[CH:24]=[CH:23][C:22]([C:20]#[N:21])=[CH:31][CH:30]=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 67006432HCID 67006432, compound

Product 1

HCID 67006171HCID 67006171, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

(2R,3R)-2-(3-chloro-4-cyano-2-ethylphenylamino)-3-hydroxybutanoic acid (700 mg, 2.48 mmol), 4-cyanobenzohydrazide (439 mg, 2.73 mmol) and anhydrous THF (20 mL) were placed in a 50 mL round bottomed flask and the mixture was cooled to −15° C. 1-Hydroxybenzotriazole hydrate (335 mg, 2.48 mmol) was added to the mixture together with N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide HCl (589 mg, 3.07 mmol) at −15° C. followed by triethylamine (0.43 mL, 3.07 mmol). The reaction mixture was maintained at −15° C. and stirred for 1 h after which, stirring continued overnight while the mixture slowly warmed to room temperature. After 18 h, the mixture was filtered under vacuum and the residue washed with THF (30 mL). The THF solution was concentrated to ca. 10 mL, whereupon EtOAc (40 mL) was added followed by water (30 mL). The phases were partitioned and the organic phase washed with water (15 mL), brine (15 mL), dried (Na2SO4), filtered and concentrated to furnish a light brown solid. Purification by flash column chromatography [EtOAc-hexanes (4:1) as eluent] afforded the title compound as a white solid (890 mg, 62%). 1H NMR (500 MHz, acetone-d6, δ in ppm) δ 9.67 (br s, 2H), 8.11 (d, J=8.8 Hz, 2H), 7.96 (d, J=8.8 Hz, 2H), 7.52 (d, J=8.8 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 5.66 (d, J=7.03 Hz, 1H), 4.62 (br s, 1H), 4.32-4.22 (m, 1H), 4.18 (dd, J=1.7 Hz, 7.4 Hz, 1H), 2.94-2.77 (m, 2H) 1.39 (d, J=6.2 Hz, 3H), 1.17 (t, J=7.6 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was maintained at −15° C.
  2. stirringstirring
  3. waitcontinued overnight while the mixture
  4. temperatureslowly warmed to room temperature
  5. waitAfter 18 h
  6. filtrationthe mixture was filtered under vacuum
  7. washthe residue washed with THF (30 mL)
  8. concentrationThe THF solution was concentrated to ca. 10 mL, whereupon EtOAc (40 mL)
  9. additionwas added
  10. customThe phases were partitioned
  11. washthe organic phase washed with water (15 mL), brine (15 mL)
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto furnish a light brown solid
  16. customPurification by flash column chromatography [EtOAc-hexanes (4:1) as eluent]

Sources & evidence

ORD record
ord-45b68ed0b1b34ec9ab2ec88769fddc77
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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