Dimethylformamide → 5-Fluoro-3-[2-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-pyridazin-4-yl)-butyrylamino]-4-oxo-pentanoic acid tert-butyl ester

HRID 446889ノート

反応式

HRID 446889 の反応式
[C:1]([O:5][C:6](=[O:14])[CH2:7][CH:8]([NH2:13])[CH:9]([OH:12])[CH2:10][F:11])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=N[C:25]2[CH:26]=[CH:27][CH:28]=N[C:24]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:39]([N:41](CC)CC)C.CC(OI1(OC(C)=O)(OC(C)=O)[O:59][C:57](=O)[C:56]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]1=2)=O.[CH3:68][N:69]([CH:71]=[O:72])C>C(O)(C)C.ClCCl>[C:1]([O:5][C:6](=[O:14])[CH2:7][CH:8]([NH:13][C:57](=[O:59])[CH:56]([C:51]1[C:71](=[O:72])[N:69]([C:68]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:41]=[CH:39][C:52]=1[CH3:53])[CH2:55][CH3:54])[C:9](=[O:12])[CH2:10][F:11])([CH3:4])([CH3:2])[CH3:3]

参加物

8

反応物 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 159087TriacetoxyperiodinaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 108566723-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester

生成物 1

HCID 866364985-Fluoro-3-[2-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-pyridazin-4-yl)-butyrylamino]-4-oxo-pentanoic acid tert-butyl ester収率 72%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A mixture of the carboxylic acid derivative of Preparation 1-5) (271 mg, 1.00 mmol), 3-amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (see Tetrahedron Letters, 1994, 35(52), 9693-9696, 248 mg, 1.2 eq) and HATU (494 mg, 1.3 eq) was cooled to 0° C., triethylamine (0.56 mL, 4.0 eq) was added thereto in DMF solvent (5 mL), and the mixture was reacted for one day. The solvent was distilled under reduced pressure. The residue was extracted with ethyl acetate (30 mL×2), washed with water, aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution, dried (anhydrous Na2SO4), and concentrated under reduced pressure. To this compound and Dess-Martin reagent (848 mg, 2.0 eq) was added anhydrous dichloromethane (4 mL), which was then stirred for 1 h at room temperature. The reaction was stopped by isopropyl alcohol (1 mL). The solid was removed by celite filtration under reduced pressure, and extracted with ethyl acetate (20 mL×2). The extract was washed with water, saturated aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution, dried (anhydrous Na2SO4), and concentrated under reduced pressure. The residue was separated by column chromatography (30-40% ethyl acetate-hexane) to give 330 mg (72%) of the title compound.

後処理

  1. distillationThe solvent was distilled under reduced pressure
  2. extractionThe residue was extracted with ethyl acetate (30 mL×2)
  3. washwashed with water, aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution
  4. dry with materialdried (anhydrous Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe solid was removed by celite filtration under reduced pressure
  7. extractionextracted with ethyl acetate (20 mL×2)
  8. washThe extract was washed with water, saturated aqueous sodium hydrogen carbonate solution and aqueous sodium chloride solution
  9. dry with materialdried (anhydrous Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was separated by column chromatography (30-40% ethyl acetate-hexane)

出典と根拠

ORDレコード
ord-732530e5fc234186853ebc6bfd917788
出典データセット
uspto-grants-2013_07
特許番号
US08481537B2

反応ノート

読み込み中…