4-Toluenesulfonyl chloride → [(4R/S)-3-Fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

HRID 15120

반응식

HRID 15120 반응식
[F:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][C:8](=[O:17])[N:9]3[CH2:13][C:12]([OH:16])([CH2:14][OH:15])[C:11]=1[C:10]=23.FC1C=NC2C=CC(=O)N3CC(=C)C=1C=23.C(N(CC)CC)C.[C:40]1([CH3:50])[CH:45]=[CH:44][C:43]([S:46](Cl)(=[O:48])=[O:47])=[CH:42][CH:41]=1.C([Sn](=O)CCCC)CCC>ClCCl.O1CCCC1.CN(C)C=O.O>[CH3:50][C:40]1[CH:45]=[CH:44][C:43]([S:46]([O:15][CH2:14][C:12]2([OH:16])[C:11]3=[C:2]([F:1])[CH:3]=[N:4][C:5]4[CH:6]=[CH:7][C:8](=[O:17])[N:9]([C:10]=43)[CH2:13]2)(=[O:48])=[O:47])=[CH:42][CH:41]=1

참가 물질

8

반응물 5

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 61221Dibutyltin oxideHCID 23634273(4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneHCID 675275493-Fluoro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

생성물 1

HCID 131728163[(4R/S)-3-Fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

시약·촉매·용매 2

HCID 962Water용매HCID 86642945dichloromethane tetrahydrofuran DMF용매

실험 절차

A mixture of (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (553 mg, 2.3 mmol) (racemic material, prepared from 3-fluoro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one using AD mix alpha/beta in a similar manner to Example 1(e) Method A) in dichloromethane/tetrahydrofuran/N,N-dimethylformamide (19 ml19 ml/2 ml) was treated with triethylamine (0.5 ml, 3.5 mmol), para-toluenesulphonyl chloride (446 mg, 2.3 mmol) and dibutyltin oxide (29 mg, 0.1 mmol) and stirred at room temperature overnight. Water was then added, the organic phase was separated and washed with saturated aqueous sodium bicarbonate, separated, dried over magnesium sulphate and evaporated under vacuum. The residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane then 0-10% methanol in ethyl acetate affording a white solid (321 mg, 35%).

후처리

  1. customthe organic phase was separated
  2. washwashed with saturated aqueous sodium bicarbonate
  3. customseparated
  4. dry with materialdried over magnesium sulphate
  5. customevaporated under vacuum
  6. customThe residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane

출처 및 근거

ORD 기록
ord-90c35ecce929460ca5f37a3bf5782e19
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07732460B2

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