Triethylamine → HCID 67006811, compound

HRID 470840

Reaction equation

HRID 470840 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].[Br:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH2:27])=[O:25])=[CH:22][CH:21]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CCN(CC)CC>C1COCC1>[Br:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH:27][C:12](=[O:14])[C@H:11]([NH:10][C:4]2[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=2[CH3:18])[C@@H:15]([OH:17])[CH3:16])=[O:25])=[CH:22][CH:21]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 222194-BromobenzohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine

Product 1

HCID 67006811HCID 67006811, compoundYield 76.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

(2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (5.0 g, 18.6 mmol), 4-bromobenzhydrazide (CAS 5933-32-4, 4.0 g, 18.6 mmol) and 1-Hydroxybenzotriazole hydrate (2.52 g, 18.6 mmol) were placed in a 250 mL round bottomed flask. Anhydrous THF (120 mL) was added and the mixture was cooled to −20° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide HCl (5.35 g, 27.9 mmol) was added, Followed by Et3N (3.9 mL, 28.0 mmol). The reaction mixture was stirred at −20° C. for 1 h and room temperature for overnight. The reaction was quenched by adding water and extracted with EtOAc, which was washed with 5% aqueous NaOH, water, brine and dried over Na2SO4. The extracts were filtered and the filtrate was concentrated to provide a brown solid, which was purified by flash chromatography washed with 80% EtOAc in hexanes to afford the title compound (6.6 g, 76%). 1H NMR (400 MHz, acetone-d6, δ in ppm) 7.87 (d, J=8.6 Hz, 2H), 7.71 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 1H), 6.67 (d, J=8.6 Hz, 1H), 5.55 (d, J=7.4 Hz, 1H), 4.39 (m, 1H), 4.10 (dd, J=3.3, 7.4 Hz, 1H), 2.36 (s, 3H), 1.35 (d, J=6.4 Hz, 3H).

Workup

  1. customThe reaction was quenched
  2. additionby adding water
  3. extractionextracted with EtOAc, which
  4. washwas washed with 5% aqueous NaOH, water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe extracts were filtered
  7. concentrationthe filtrate was concentrated
  8. customto provide a brown solid, which
  9. customwas purified by flash chromatography
  10. washwashed with 80% EtOAc in hexanes

Sources & evidence

ORD record
ord-ca5560ab2d324a59a4d6fdad2ecc5df8
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Linked notes

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