Triethylamine → (S)-2',3'-di-O-acetyl-2-chloro-5'-O-methyl-N-[2-(methylmethoxy)-1-pyrrolidinyl]adenosine

HRID 1082099노트

반응식

HRID 1082099 반응식
[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][CH3:16])[O:7][C@H:6]1[N:17]1[CH:25]=[N:24][C:23]2[C:18]1=[N:19][C:20]([Cl:27])=[N:21][C:22]=2Cl)(=[O:3])[CH3:2].[NH2:28][N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1COC.C(N(CC)CC)C.[O:44]1CCO[CH2:46][CH2:45]1>ClCCl>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][CH3:16])[O:7][C@@H:6]1[N:17]1[C:18]2[N:19]=[C:20]([Cl:27])[N:21]=[C:22]([NH:28][N:29]3[CH2:33][CH2:32][CH2:31][CH:30]3[O:44][CH2:45][CH3:46])[C:23]=2[N:24]=[CH:25]1)(=[O:3])[CH3:2]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 7156993(S)-(-)-1-Amino-2-(methoxymethyl)pyrrolidineHCID 110698082,6-dichloro-9-(2,3-di-O-acetyl-5-O-methyl-beta-D-ribofuranosyl)-purine

생성물 1

HCID 86750102(S)-2',3'-di-O-acetyl-2-chloro-5'-O-methyl-N-[2-(methylmethoxy)-1-pyrrolidinyl]adenosine수율 18%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

9-(2',3'-Di-O-acetyl-5'-O-methyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.3 g, 3.1 mmol), (S)-N-amino-2-(methoxymethyl)pyrrolidine (0.81 g, 6.2 mmol) and triethylamine (0.63 g, 6.2 mmol) were dissolved in dioxan. After stirring for 20 h the reaction mixture was diluted with dichloromethane (150 ml) and washed with water (2×75 ml). The organic phase was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography eluting with a mixture of dichloromethane and 10% ammonia in ethanol (97:3) to afford (S)-2',3'-di-O-acetyl-2-chloro-5'-O-methyl-N-[2-(methylmethoxy)-1-pyrrolidinyl]adenosine (0.28 g, 18%) as a foam. 1H-NMR (400 MHz, CDCl3) δ1.70-2.10 (4H, m, pyrrolidine C--H), 2.05 (3H, s, --OCOCH3), 2.18 (3H, S, --OCOCH3), 2.85 (1H, m, pyrrolidine C--H), 3.10 (1H, br, pyrrolidine C--H), 3.22 (3H, s, --OCH3), 3.35-3.70 (8H, m, H-5'a and H-5'b, --OCH3, pyrrolidine, --CH2 --), 4.32 (1H, s, H-4'), 5.55 (1H, d, H-3'), 5.75 (1H, t, H-3'), 6.32 (1H, d, H-1'), 8.17 (1H, s, H-8). HPLC retention time 15.57 min. (gradient elution over 25 min.; 20-80% acetonitrile/0.1% TFA in water).

후처리

  1. washwashed with water (2×75 ml)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was purified by flash chromatography
  5. washeluting with a mixture of dichloromethane and 10% ammonia in ethanol (97:3)

출처 및 근거

ORD 기록
ord-ed77c9310f40425e929d1f0a4a33a452
출처 데이터셋
uspto-grants-1996_12
특허 번호
US05589467

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