Diisopropylethylamine → tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate

HRID 1782183Notes

Reaction equation

HRID 1782183 reaction equation
C(N(C(C)C)CC)(C)C.[C:10]([NH:17][C@H:18]([C:22]([OH:24])=O)[CH:19]([CH3:21])[CH3:20])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].NC(C(C)C)C(=O)[CH2:28][CH2:29][N:30]([C:36]1[CH:41]=[CH:40][N:39]=[C:38]([C:42]2[O:46][N:45]=[C:44]([C:47]3[C:52]([Cl:53])=[CH:51][CH:50]=[CH:49][C:48]=3[Cl:54])[CH:43]=2)[CH:37]=1)[C:31](=[O:35])[CH:32]([Cl:34])[Cl:33]>C(Cl)Cl>[Cl:34][CH:32]([Cl:33])[C:31]([N:30]([CH2:29][CH2:28][C:22](=[O:24])[CH:18]([NH:17][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[CH:19]([CH3:20])[CH3:21])[C:36]1[CH:41]=[CH:40][N:39]=[C:38]([C:42]2[O:46][N:45]=[C:44]([C:47]3[C:48]([Cl:54])=[CH:49][CH:50]=[CH:51][C:52]=3[Cl:53])[CH:43]=2)[CH:37]=1)=[O:35]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 12002082N-(4-amino-5-methyl-3-oxohexyl)-2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamide

Product 1

HCID 57588429tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Pybop (164 mg, 0.32 mmol), diisopropylethylamine (50 mg, 0.39 mmol) and N-boc-L-valine (69 mg, 0.32 mmol) were added to a solution of N-(4-amino-5-methyl-3-oxohexyl)-2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamide (Cpd. No. 3, lot 2, 75 mg, 0.11 mmol) in methylene chloride (5 mL) at 0° C. The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was then diluted with methylene chloride (15 mL) and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by prep-scale reverse phase high performance liquid chromatography to provide tert-butyl 6-(2,2-dichloro-N-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-yl)acetamido)-2-methyl-4-oxohexan-3-ylcarbamate (Cpd. No. 49,100 mg) as a white solid. 1H NMR (CDCl3): 8.86 (d, 1H), 7.98 (s, 1H), 7.45-7.33 (m, 5H), 5.98 (s, 1H), 5.66 (br s, 1H), 4.98 (br s, 1H), 4.55-4.51 (m, 2H), 4.11-4.02 (m, 3H), 3.00-2.93 (m, 2H), 2.20 (m, 1H), 1.48 (s, 9H), 1.09 (d, 3H), 0.90 ppm (d, 3H).

Workup

  1. customat 0° C
  2. washwashed successively with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by prep-scale reverse phase high performance liquid chromatography

Sources & evidence

ORD record
ord-aa467d45ccf34f83b406c64b885cea87
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

Loading…