Dimethylformamide → 4-{(S)-4-tert-butoxycarbonyl-2-[(6-methyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

HRID 553827Notes

Reaction equation

HRID 553827 reaction equation
[CH:1]1[CH:6]=[C:5]2N=NN(O)[C:4]2=[CH:3][CH:2]=1.O.[CH3:12][CH2:13][N:14]=[C:15]=[N:16][CH2:17][CH2:18]CN(C)C.Cl.[CH2:24]([O:26][C:27]([N:29]1[CH2:34][CH2:33][N:32]([C:35](=[O:47])[C@@H:36]([NH2:46])[CH2:37][CH2:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:31][CH2:30]1)=[O:28])[CH3:25].[NH4+].[Cl-].CN([CH:53]=[O:54])C>>[CH2:24]([O:26][C:27]([N:29]1[CH2:30][CH2:31][N:32]([C:35](=[O:47])[C@@H:36]([NH:46][C:53]([C:17]2[CH:18]=[C:13]([CH3:12])[N:14]=[C:15]([C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][CH:6]=3)[N:16]=2)=[O:54])[CH2:37][CH2:38][C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:33][CH2:34]1)=[O:28])[CH3:25]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66651766ethyl 4-[(2S)-2-amino-5-tert-butoxy-5-oxopentanoyl]piperazine-1-carboxylate

Product 1

HCID 674634794-{(S)-4-tert-butoxycarbonyl-2-[(6-methyl-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

Procedure

Intermediate 86.2 (214 mg), HOBT hydrate (168 mg) and EDCI hydrochloride (210 mg) were dissolved in DMF (7 ml). After 15 min stirring, 4-((S)-2-amino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl ester (377 mg) was added and the stirring was continued overnight at RT. A saturated NH4Cl solution was added and the mixture was extracted with EA. The org. phases were dried (Na2SO4) and evaporated off. Column chromatography (EA/Hept 1/3 to 1/1) of the crude offered the compound still contaminated by some starting material. It was then taken up in EA and washed with a Na2CO3 solution, dried and evaporated off to give 462 mg of the pure desired compound.

Workup

  1. waitthe stirring was continued overnight at RT
  2. extractionthe mixture was extracted with EA
  3. dry with materialphases were dried (Na2SO4)
  4. customevaporated off
  5. washwashed with a Na2CO3 solution
  6. customdried
  7. customevaporated off

Sources & evidence

ORD record
ord-0610ada155494cdbb256f1f17b3f32d4
Source dataset
uspto-grants-2011_11
Patent number
US08048881B2

Reaction notes

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