Ethyl Acetate → HCID 22950007, compound

HRID 1700968Notes

Reaction equation

HRID 1700968 reaction equation
[CH3:1][C:2]([CH3:41])([CH3:40])[C@H:3]([NH:15][C:16]([C@H:18]([CH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:28]([F:39])[CH:27]=1)[CH2:19][C:20](O)=[O:21])=[O:17])[C:4]([NH:6][C@@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:5].C(N(C(C)C)CC)(C)C.Cl.[NH2:52][OH:53].C(OCC)(=O)C>CN(C)C=O>[CH3:1][C:2]([CH3:40])([CH3:41])[C@H:3]([NH:15][C:16](=[O:17])[C@H:18]([CH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:28]([F:39])[CH:27]=1)[CH2:19][C:20]([NH:52][OH:53])=[O:21])[C:4]([NH:6][C@@H:7]([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH3:8])=[O:5]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531Diisopropylethylamine2×HCID 443297Hydroxyamine hydrochlorideHCID 59875738HCID 59875738, compound

Product 1

HCID 22950007HCID 22950007, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

N-[(Dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-ylmethylene]-N-methylmethaninium hexafluorophosphate N-oxide (740 mg, 1.95 mmol) was added to a stirred solution of (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3-fluoro-4-phenoxyphenyl)hexanoic acid (Preparation 5) (731 mg, 1.30 mmol) and diisopropylethylamine (220 μL, 1.30 mmol) in anhydrous dimethylformamide (10 mL) at 0° C. under nitrogen. After 25 min, hydroxylamine hydrochloride (271 mg, 3.90 mmol) was added followed by diisopropylethylamine (880 μL, 5.20 mmol). The resulting mixture was stirred at 20° C. for 16 h, poured into ethyl acetate (150 mL) and washed with pH 7 phosphate buffer solution (3×50 mL), saturated aqueous sodium chloride (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was recrystallised from dichloromethane/diisopropyl ether to give the title compound as a colourless solid (275 mg, 24%). Further purification of a sample (130 mg) by preparative hplc (Phenomenex C18 Magellan column, 150×20 mm, 5μ packing, 20 mL/min acetonitrile:aqueous phosphate buffer (8.3 mM, pH 7.2)=1:1, retention time 13.5 min), then trituration with diisopropyl ether, filtration and drying in vacuo at 50° C. gave 50 mg of a white solid.

Workup

  1. washwashed with pH 7 phosphate buffer solution (3×50 mL), saturated aqueous sodium chloride (50 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was recrystallised from dichloromethane/diisopropyl ether

Sources & evidence

ORD record
ord-a1dc20401a034653a1a3f1f098325c5a
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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