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

Reaction equation

HRID 241533 reaction equation
[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]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 60749Gemcitabine HydrochlorideHCID 2724699PyBOPHCID 66771690HCID 66771690, compound2×

Product 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

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-72b95fdc84c042fba070fcfcc5d49b7a
Source dataset
uspto-grants-2014_02
Patent number
US08653048B2

Linked notes

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