N-methyl-2-pyrrolidone → HCID 86625846, compound

HRID 644144Notes

Reaction equation

HRID 644144 reaction equation
CN1CCCC1=O.O.[C:9]([O:13][C:14]([NH:16][C@H:17]([C:22]([OH:24])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])=[O:15])([CH3:12])([CH3:11])[CH3:10].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:37][C:38](=[N:68]O)[C:39]1[CH:67]=[CH:66][C:42]([O:43][CH2:44][CH2:45][CH2:46][CH:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][CH2:55][O:56][C:57]3[CH:65]=[CH:64][C:60]([C:61]([NH2:63])=[O:62])=[CH:59][CH:58]=3)[CH2:49][CH2:48]2)=[CH:41][CH:40]=1>O.C(OCC)(=O)C>[NH2:68][C:38](=[N:37][O:23][C:22](=[O:24])[C@@H:17]([NH:16][C:14]([O:13][C:9]([CH3:11])([CH3:10])[CH3:12])=[O:15])[CH2:18][CH:19]([CH3:20])[CH3:21])[C:39]1[CH:67]=[CH:66][C:42]([O:43][CH2:44][CH2:45][CH2:46][CH:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][CH2:55][O:56][C:57]3[CH:58]=[CH:59][C:60]([C:61]([NH2:63])=[O:62])=[CH:64][CH:65]=3)[CH2:49][CH2:48]2)=[CH:41][CH:40]=1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidone2×HCID 682631,1'-CarbonyldiimidazoleHCID 12373896N-Boc-L-Leucine HydrateHCID 86625843HCID 86625843, compound

Product 1

HCID 86625846HCID 86625846, compoundYield 47.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an N-methyl-2-pyrrolidone (5 mL) solution of 0.23 g of N-(tert-butoxycarbonyl)-L-leucine monohydrate was added 0.34 g of 1,1′-carbonyldiimidazole at room temperature, which was then stirred at the same temperature for 1 hour and 30 minutes. An N-methyl-2-pyrrolidone (5 mL) solution of 0.20 g of 4-{3-[4-(3-{4-[amino(hydroxyimino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}benzamide=oxime was added to the mixture at room temperature, which was then stirred at the same temperature for 5 hours. The reaction mixture was added to a mixture of ethyl acetate and water. The organic layer was separated, washed with a saturated sodium chloride aqueous solution, and then dried with anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The resultant residue was purified using silica gel column chromatography (eluent; chloroform:methanol=10:1) to provide 0.14 g of 4-(3-{4-[3-(4-{amino[(2S)-2-(tert-butoxycarbonyl)amino-4-methylpentanoyloxyimino]methyl}phenoxy)propyl]-1-piperidinyl}propoxy)benzamide=O-[(2S)-2 (tert-butoxycarbonyl)amino-4-methylpentanoyl]oxime as white solid form.

Workup

  1. stirringwhich was then stirred at the same temperature for 5 hours
  2. customThe organic layer was separated
  3. washwashed with a saturated sodium chloride aqueous solution
  4. dry with materialdried with anhydrous magnesium sulfate
  5. distillationby distilling off the solvent under reduced pressure
  6. customThe resultant residue was purified

Sources & evidence

ORD record
ord-eaf0717b4ff549d58884f292343c8eb3
Source dataset
uspto-grants-2010_04
Patent number
US07700623B2

Reaction notes

Loading…