Citric Acid → Acetic acid 2-{3-[(4-{amino[benzoylimino]methyl}phenylamino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy)ethyl ester

HRID 2089636

反応式

HRID 2089636 の反応式
CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:16][C:17](=[N:51][C:52](=[O:59])[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:18]1[CH:23]=[CH:22][C:21]([NH:24][CH:25]([C:38]2[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[C:40]([O:46][CH2:47][CH2:48][OH:49])[C:39]=2[F:50])[C:26]2[NH:30][C:29](=[O:31])[N:28]([C:32]3[N:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[N:27]=2)=[CH:20][CH:19]=1.C(O)(=O)[CH2:61][C:62](CC(O)=O)(C(O)=O)[OH:63].P([O-])([O-])(O)=O.[Na+].[Na+]>CN(C1C=CN=CC=1)C.C1COCC1.C(OCC)(=O)C.O.CN(C=O)C.ClCCl.C(O)(=O)C.C(N(CC)CC)C>[NH2:16][C:17](=[N:51][C:52](=[O:59])[C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[C:18]1[CH:23]=[CH:22][C:21]([NH:24][CH:25]([C:26]2[NH:30][C:29](=[O:31])[N:28]([C:32]3[N:33]=[CH:34][CH:35]=[CH:36][N:37]=3)[N:27]=2)[C:38]2[C:39]([F:50])=[C:40]([CH:41]=[C:42]([O:44][CH3:45])[CH:43]=2)[O:46][CH2:47][CH2:48][O:49][C:62](=[O:63])[CH3:61])=[CH:20][CH:19]=1

参加物

13

反応物 4

HCID 311Citric AcidHCID 24203Sodium Phosphate, DibasicHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 136334022N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide

生成物 1

HCID 136334025Acetic acid 2-{3-[(4-{amino[benzoylimino]methyl}phenylamino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy)ethyl ester

試薬・触媒・溶媒 8

HCID 142844-(Dimethylamino)pyridine触媒HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Under nitrogen atmosphere, triethylamine (6.97 mL) was added under ice-cooling to a mixture of acetic acid (601 mg), TFFH (2.64 g), and dichloromethane (50 mL), and the resulting mixture was stirred for 1 hour. To the resulting mixture, a mixture of N-[1-amino-1-(4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}phenyl)methylidene]benzamide (Example 1a, 3 g), DMAP (5 mg), and DMF (50 mL) was added dropwise. After stirring the resulting mixture overnight at room temperature, the solvent in the mixture was distilled off under reduced pressure. The residue obtained was dissolved in a small amount of THF, and ethyl acetate (300 mL) and water (100 mL) were added to the resulting mixture. After a buffer (prepared by adding 37 mL of 0.1 M citric acid to 63 mL of 0.2 M disodium hydrogen phosphate) was added to the resulting mixture to adjust the pH to 6, the mixture was shaken, and the organic layer was collected. The organic layer was sequentially washed twice with water (100 mL) and with saturated aqueous sodium chloride solution (100 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (2.16 g).

後処理

  1. additionwas added dropwise
  2. stirringAfter stirring the resulting mixture overnight at room temperature
  3. distillationthe solvent in the mixture was distilled off under reduced pressure
  4. customThe residue obtained
  5. additionwere added to the resulting mixture
  6. additionwas added to the resulting mixture
  7. stirringthe mixture was shaken
  8. customthe organic layer was collected
  9. washThe organic layer was sequentially washed twice with water (100 mL) and with saturated aqueous sodium chloride solution (100 mL)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationThe resulting mixture was filtered
  12. customthe filtrate obtained
  13. concentrationwas concentrated under reduced pressure
  14. customThe residue obtained
  15. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

出典と根拠

ORDレコード
ord-1255a8d082664ac88e2bcf99dea29586
出典データセット
uspto-grants-2013_05
特許番号
US08436009B2

関連ノート

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