Diisopropylethylamine → {(S)-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-3-methyl-butyl}-carbamic acid t-butyl ester

HRID 19418

反応式

HRID 19418 の反応式
O.[C:2]([O:6][C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])([CH3:5])([CH3:4])[CH3:3].Cl.[OH:19][C@@H:20]([CH2:50]O)[CH2:21][N:22]1[CH:26]=[CH:25][C:24]([NH:27]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:23]1.[CH:52](N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:2]([O:6][C:7](=[O:8])[NH:9][C@H:10]([C:15](=[O:17])[NH:27][C:24]1[CH:25]=[CH:26][N:22]([CH2:21][C:20]([OH:19])([CH3:50])[CH3:52])[N:23]=1)[CH2:11][CH:12]([CH3:13])[CH3:14])([CH3:3])([CH3:4])[CH3:5]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 12373896N-Boc-L-Leucine HydrateHCID 66899094HMS5552 HCl

生成物 1

HCID 67504285{(S)-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-3-methyl-butyl}-carbamic acid t-butyl ester収率 100%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of N-t-butoxycarbonyl-(L)-leucine mono-hydrate (2.81 g, 11.28 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 2.02 g, 13 mmol) in N,N-dimethylformamide (15 mL) was treated with N,N-diisopropylethylamine (3.5 mL, 20 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (8.84 g, 20 mmol) and stirred at room temperature for 12 h. At this time the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and a concentrated ammonium chloride solution. The layers were separated and the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The mixture was filtered and concentrated in vacuo and the residue purified by ISCO flash chromatography (RediSep silica 120 g, 20% to 80% ethyl acetate/hexanes) which afforded {(S)-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-3-methyl-butyl}-carbamic acid t-butyl ester (4.15 g, 100%) as a white solid.

後処理

  1. concentrationAt this time the mixture was concentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate
  3. customThe layers were separated
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by ISCO flash chromatography (RediSep silica 120 g, 20% to 80% ethyl acetate/hexanes) which

出典と根拠

ORDレコード
ord-4827150e902b432aabb31ece66583d4f
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

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