Water → Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoate

HRID 241530

반응식

HRID 241530 반응식
[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([C@@H:9]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C:10]2([F:18])[F:17])[CH:2]=1.Cl.[CH2:20]([O:32][C:33]([C:35]1[CH:43]=[CH:42][CH:41]=[CH:40][C:36]=1[C:37](O)=[O:38])=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:20]([O:32][C:33](=[O:34])[C:35]1[CH:43]=[CH:42][CH:41]=[CH:40][C:36]=1[C:37](=[O:38])[NH:8][C:7]1[CH:1]=[CH:2][N:3]([C@H:9]2[C:10]([F:17])([F:18])[C@H:11]([OH:16])[C@@H:12]([CH2:14][OH:15])[O:13]2)[C:4](=[O:5])[N:6]=1)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]

참가 물질

7

반응물 4

HCID 962WaterHCID 60749Gemcitabine HydrochlorideHCID 88948Dodecyl phthalateHCID 2724699PyBOP

생성물 1

HCID 60201196Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoate수율 26.7%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

Gemcitabine hydrochloride (0.7 g, 2.34 mmol), 2-(dodecyloxycarbonyl)benzoic acid (1.02 g, 3.04 mmol), (Benzotriazol-1-yl-oxy)tripyrrolidinylphosphonium hexafluorophosphate (1.34 g, 2.57 mmol), and 4-dimethylaminopyridine (428 mg, 3.51 mmol) were dissolved in N,N-dimethylformamide (10 mL) and stirred overnight at room temperature. The reaction mixture was poured into water, and then extracted three times with ethyl acetate. The isolated organic phase was dried with anhydrous Na2SO4. The solvent was removed by vaporizing under reduced pressure. The residue was purified by silica column chromatography (developing agent: dichloromethane/methanol=30/1) to produce 362.5 mg of Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoate. LC purity 98% (UV254). LC-MS m/z 580 [M+H]+ (molecular formula: C29H39F2N3O7, molecule weight: 579). The structure and characterization data of the compound were shown in Table 1.

후처리

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe isolated organic phase was dried with anhydrous Na2SO4
  3. customThe solvent was removed
  4. customThe residue was purified by silica column chromatography (developing agent: dichloromethane/methanol=30/1)

출처 및 근거

ORD 기록
ord-20473a9dd9354595a0c21daec6f1d3f8
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653048B2

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