Triethylamine → 3,4-dichloro-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)benzohydrazide

HRID 470839노트

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HRID 470839 반응식
[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].[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[Cl:30])[C:23]([NH:25][NH2:26])=[O:24].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[Cl:30])[C:23]([NH:25][NH:26][C:12](=[O:14])[C@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:18])[C@@H:15]([OH:17])[CH3:16])=[O:24]

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 3119963,4-DichlorobenzhydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine

생성물 1

HCID 670064343,4-dichloro-N'-((2R,3S)-2-(3-chloro-4-cyano-2-methylphenyl-amino)-3-hydroxybutanoyl)benzohydrazide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-15 °C

실험 절차

(2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid (1.0 g, 3.7 mmol), 3,4-dichlorobenzohydrazide (CAS 28036-91-1, 763 mg, 3.7 mmol) and anhydrous THF (100 mL) were placed in a 500 mL round bottomed flask and the mixture was cooled to −15° C., 1-Hydroxybenzotriazole hydrate (502.8 mg, 3.7 mmol) was added to the mixture together with N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide HCl (1.4 g, 7.4 mmol) and triethylamine (1.03 mL, 7.4 mmol) at −15° C. 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 (50 mL). The THF solution was concentrated to ca. 10 mL, whereupon ethyl acetate (200 mL) was added followed by water (100 mL). The phases were partitioned and the organic phase washed with water (50 mL), brine (50 mL), dried (Na2SO4), filtered and concentrated to furnish a light brown solid. 1H NMR (500 MHz, acetone-d6, δ in ppm) 8.10 (d, J=2.1 Hz, 1H), 7.90 (dd, J=2.2 Hz, 8.3 Hz, 1H), 7.74 (d, J=8.3 Hz, 1H), 7.55 (d, J=8.5 Hz, 1H), 6.71 (d, J=8.5 Hz, 1H), 5.57 (d, J=6.8 Hz, 1H), 4.44-4.36 (m, 1H), 4.16-4.10 (m, 1H), 2.88-2.80 (m, 1H), 2.37 (s, 3H), 1.37 (d, J=6.3 Hz, 3H).

후처리

  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 (50 mL)
  8. concentrationThe THF solution was concentrated to ca. 10 mL, whereupon ethyl acetate (200 mL)
  9. additionwas added
  10. customThe phases were partitioned
  11. washthe organic phase washed with water (50 mL), brine (50 mL)
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto furnish a light brown solid

출처 및 근거

ORD 기록
ord-85412756abb047d6a1e4c62ca968664c
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629167B2

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