Sodium Hydroxide → N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide

HRID 133807

Reaction equation

HRID 133807 reaction equation
[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](/[C:29]([OH:31])=O)\[CH3:28])[CH3:24])=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl.[CH3:36][NH:37][O:38][CH3:39].[OH-].[Na+]>O1CCCC1.O.[Cl-].[Na+].O>[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](\[CH3:28])/[C:29]([N:37]([O:38][CH3:39])[CH3:36])=[O:31])[CH3:24])=[O:22])[C:17]([CH3:18])([CH3:20])[CH3:19])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 3

HCID 14798Sodium Hydroxide2×HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6918637N,beta,beta-Trimethyl-L-phenylalanyl-N-((1S,2E)-3-carboxy-1-(1-methylethyl)-2-buten-1-yl)-N,3-dimethyl-L-valinamide

Product 1

HCID 11656496N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamideYield 95%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide (473 mg, 1 mmol, WO 99/32509) in tetrahydrofuran (2 mL) is added a solution of N,O-dimethylhydroxylamine hydrochloride (166 mg, 1.7 mmol) in water (2 mL), adjusting the reaction mixture to pH 4.5 by adding dropwise 1.0 N sodium hydroxide solution. To this is added dropwise a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (479 mg, 2.5 mmol) in water (7 mL) over a period of 7 min, maintaining pH 4.5 by using 1.0 N sodium hydroxide solution. The reaction mixture is stirred at room temperature for 2.5 h, adjusting the pH to 6-7. To this is added brine (10 mL) and extracted with dichloromethane. The combined organic layers are washed with brine, dried (Na2SO4), filtered and concentrated to give 491 mg (95%) of the title compound as a white solid. HRMS (ESI) calcd for C29H48N4O4 (M+H+) 517.3748, found 517.3750.

Workup

  1. temperaturemaintaining pH 4.5
  2. extractionextracted with dichloromethane
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-47f1c2a29b7147a8966671c671391628
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Linked notes

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