Diisopropylethylamine → benzyl ((25)-4-((4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrazol-3-yl)amino)-1-hydroxy-4-oxobutan-2-yl)carbamate

HRID 632761

反応式

HRID 632761 の反応式
[NH2:1][C:2]1[C:6]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:5][N:4]([CH3:15])[N:3]=1.[CH2:16]([O:23][C:24]([NH:26][C@H:27]([C:32](OC)=[O:33])[CH2:28][C:29](O)=[O:30])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[BH4-].[Li+]>CN(C=O)C.C1COCC1.CO.O>[C:10]([O:9][C:8]([NH:7][C:6]1[C:2]([NH:1][C:29](=[O:30])[CH2:28][C@H:27]([NH:26][C:24](=[O:25])[O:23][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:32][OH:33])=[N:3][N:4]([CH3:15])[CH:5]=1)=[O:14])([CH3:11])([CH3:12])[CH3:13]

参加物

10

反応物 5

HCID 81531DiisopropylethylamineHCID 4148881Lithium borohydrideHCID 7021783Z-Asp-OMeHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 125470397tert-butyl (3-amino-1-methyl-1H-pyrazol-4-yl)carbamate

生成物 1

HCID 118065255benzyl ((25)-4-((4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrazol-3-yl)amino)-1-hydroxy-4-oxobutan-2-yl)carbamate収率 75.9%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of tert-butyl (3-amino-1-methyl-1H-pyrazol-4-yl)carbamate (1.0 g), (3S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutanoic acid (1.5 g) and HATU (2.2 g) in DMF (24 mL) was added diisopropylethylamine (1.2 mL), and the mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give a crude product (2.6 g). To a suspension of lithium borohydride (0.26 g) in THF (20 mL) was added a solution of the crude product (2.2 g) in methanol (10 mL) under ice-cooling, and the mixture was stirred at 0° C. for 1 hr. To the reaction mixture was added water, and the mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate, the extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.6 g).

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed successively with saturated aqueous ammonium chloride solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customto give a crude product (2.6 g)
  6. temperaturecooling
  7. stirringthe mixture was stirred at 0° C. for 1 hr
  8. concentrationthe mixture was concentrated under reduced pressure
  9. extractionThe residue was extracted with ethyl acetate
  10. washthe extract was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-9efcc5640dea49d9b96a31a821e84b48
出典データセット
uspto-grants-2016_04
特許番号
US09321757B2

関連ノート

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