Diisopropylethylamine → HCID 9946511, compound

HRID 1279784Notes

Reaction equation

HRID 1279784 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:16][CH:17]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.[N:41]1([O:50]C(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.NO>CN(C)C=O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:16][CH:17]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=2)[CH2:11][C:12]([NH:41][OH:50])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 443297Hydroxyamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 60077644HCID 60077644, compound

Product 1

HCID 9946511HCID 9946511, compoundYield 14.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-[4-(ethoxycarbonyl)-1,3-oxazol-2-yl]hexanoic acid (Preparation 63) (130 mg, 0.39 mmol) and N,N-diisopropylethylamine (67 μl, 0.39 mmol) in N,N-dimethylformamide (6 ml) was treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (220 mg, 0.58 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 45 minutes. Further N,N-diisopropylethylamine (270 μl, 1.54 mmol) was then added, followed by hydroxylamine hydrochloride (80 mg, 1.16 mmol) and the mixture was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and pH 7 aqueous buffer. The organic layer was separated, washed sequentially with water and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (99:1) gradually changing to dichloromethane:methanol (98:2) to afford the title compound (20 mg).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate and pH 7 aqueous buffer
  4. customThe organic layer was separated
  5. washwashed sequentially with water and brine
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol (99:1)

Sources & evidence

ORD record
ord-d6232597038449c2b3bbcc3729a4eed0
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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