Dimethylformamide → N2-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-N-3-dodecylpyrazine-2,3-dicarboxamide

HRID 241533

반응식

HRID 241533 반응식
[CH:1]1[C:7](N)=[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]([NH:32][C:33]([C:35]1[C:36]([C:41]([OH:43])=O)=[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]CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:55]2C=CC=C[C:54]=2N=N1.C[N:78](C)C=O>CN(C)C1C=CN=CC=1>[F:17][C:10]1([F:18])[C@H:11]([OH:16])[C@@H:12]([CH2:14][OH:15])[O:13][C@H:9]1[N:3]1[CH:2]=[CH:1][C:7]([N:32]([CH:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:54][CH3:55])[C:33]([C:35]2[C:36]([C:41]([NH2:78])=[O:43])=[N:37][CH:38]=[CH:39][N:40]=2)=[O:34])=[N:6][C:4]1=[O:5]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 60749Gemcitabine HydrochlorideHCID 2724699PyBOPHCID 66771690HCID 66771690, 화합물2회

생성물 1

HCID 66977836N2-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-N-3-dodecylpyrazine-2,3-dicarboxamide

시약·촉매·용매 1

HCID 142844-(Dimethylamino)pyridine촉매

실험 절차

Gemcitabine hydrochloride (200 mg, 0.67 mmol), 3-(dodecylcarbamoyl)pyrazine-2-carboxylic acid (325 mg, 1.01 mmol), benzotriazole-1-yl-oxytripyrrolidinylphosphonium hexafluorophosphate (327.6 mg, 0.74 mmol), and 4-dimethylaminopyridine (98 mg, 0.80 mmol) were dissolved in N,N-Dimethylformamide (10 mL) and stirred at room temperature overnight. The reaction mixture was poured into the 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=10/1) to produce 290 mg of N2-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-N-3-dodecylpyrazine-2,3-dicarboxamide (compound No. 37). LC purity 98% (UV 254). LC-MS m/z 581 [M+H]+, (molecular formula: C27H38F2N6O6, molecular weight: 580). 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=10/1)

출처 및 근거

ORD 기록
ord-72b95fdc84c042fba070fcfcc5d49b7a
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653048B2

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