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

HRID 19418

Reaction equation

HRID 19418 reaction equation
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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4827150e902b432aabb31ece66583d4f
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Linked notes

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