Trifluoroacetic acid → 3-(4-Acetoxymethyl-7-chloro-1H-indazol-5-yl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester

HRID 1985441노트

반응식

HRID 1985441 반응식
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:38])[C@H:11]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:12][C:13]1[CH:18]=[C:17]([Cl:19])[C:16]([NH2:20])=[C:15]([CH3:21])[C:14]=1[CH2:22][O:23][C:24](=[O:26])[CH3:25].[N:39](OCCC(C)C)=O.C([O-])(=O)C.[K+]>C(O)(=O)C.C(Cl)(Cl)Cl.ClCCl>[CH3:8][O:9][C:10](=[O:38])[C@H:11]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:29])[CH2:12][C:13]1[C:14]([CH2:22][O:23][C:24](=[O:26])[CH3:25])=[C:15]2[C:16](=[C:17]([Cl:19])[CH:18]=1)[NH:20][N:39]=[CH:21]2

참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acidHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 597319483-(2-acetoxymethyl-4-amino-5-chloro-3-methyl-phenyl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester

생성물 1

HCID 597319723-(4-Acetoxymethyl-7-chloro-1H-indazol-5-yl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester수율 83%

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 6212Chloroform용매HCID 6344Dichloromethane용매

실험 절차

Trifluoroacetic acid (70 μL, 0.91 mmol) was added to a solution of 3-(2-acetoxymethyl-4-amino-5-chloro-3-methyl-phenyl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester (345 mg, 0.77 mmol) in 5% acetic acid in chloroform (5.2 mL). Isoamyl nitrite (120 μL, 0.89 mmol) was added to the mixture drop-wise. Reaction mixture was stirred at room temperature for 40 minutes. Potassium acetate (300 mg, 3.1 mmol) was added to the mixture. Reaction mixture was stirred at room temperature for 45 minutes. Mixture was diluted with dichloromethane (10 mL) then washed successively with water (2×10 mL), and saturated aqueous sodium bicarbonate (2×10 mL). Organic was dried (magnesium sulfate), filtered and concentrated in vacuo. Crude product was obtained as an orange solid in 83% yield. Material was carried forward without further purification. 1H NMR (300 MHz, CDCl3): δ=8.20 (s, 1H); 7.29 (m, 5H); 7.21 (s, 1H); 5.53 (d, J=7.7, 1H); 5.40 (s, 2H); 5.04 (s, 2H); 4.67 (m, 1H); 3.74 (s, 3H); 3.34 (m, 1H); 3.21 (m, 1H); 2.02 (s, 3H). MS m/e (M+H)+=460.1.

후처리

  1. customReaction mixture
  2. customReaction mixture
  3. stirringwas stirred at room temperature for 45 minutes
  4. washthen washed successively with water (2×10 mL), and saturated aqueous sodium bicarbonate (2×10 mL)
  5. dry with materialOrganic was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customCrude product was obtained as an orange solid in 83% yield
  9. customMaterial was carried forward without further purification

출처 및 근거

ORD 기록
ord-84d1c52d5ecc48aba77e31f98a2577a7
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544680B2

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