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

HRID 241531

反応式

HRID 241531 の反応式
[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[C:36]([C:41](O)=[O:42])=[N:37][CH:38]=[CH:39][N:40]=1)=[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]([C:35]1[C:36]([C:41](=[O:42])[NH:8][C:7]2[CH:1]=[CH:2][N:3]([C@H:9]3[C:10]([F:17])([F:18])[C@H:11]([OH:16])[C@@H:12]([CH2:14][OH:15])[O:13]3)[C:4](=[O:5])[N:6]=2)=[N:37][CH:38]=[CH:39][N:40]=1)=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]

参加物

7

反応物 4

HCID 962WaterHCID 60749Gemcitabine HydrochlorideHCID 2724699PyBOPHCID 667719023-(Dodecyloxycarbonyl)pyrazine-2-carboxylic acid

生成物 1

HCID 60201199dodecyl-3-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)pyrazine-2-carboxylate収率 23.2%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

Gemcitabine hydrochloride (500 mg, 1.67 mmol), 3-(dodecyloxycarbonyl)pyrazine-2-carboxylic acid (674 mg, 2.01 mmol), (Benzotriazol-1-yl-oxy)tripyrrolidinophosphonium hexafluorophosphate (955 mg, 1.84 mmol), and 4-dimethylaminopyridine (244 mg, 2.0 mmol) were dissolved in N,N-dimethylformamide (10 mL) and stirred at room temperature overnight. The reaction mixture was poured into water, 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=40/1) to produce 225.7 mg of dodecyl-3-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)pyrazine-2-carboxylate. LC purity 98% (UV 254). LC-MS m/z 582 [M+H]+, (molecular formula: C27H37F2N5O7, molecular weight: 581). The structure and characterization data of the compound were shown in Table 1.

後処理

  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=40/1)

出典と根拠

ORDレコード
ord-df1365858c024896b155249609c159b1
出典データセット
uspto-grants-2014_02
特許番号
US08653048B2

関連ノート

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