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

HRID 553823Notes

Reaction equation

HRID 553823 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[N:13]=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]=[C:10]([C:20]([OH:22])=O)[CH:9]=1.CCN(CC)CC.[CH2:30]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:41](=[O:53])[C@@H:42]([NH2:52])[CH2:43][CH2:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:37][CH2:36]1)=[O:34])[CH3:31]>C(#N)C.O>[CH2:30]([O:32][C:33]([N:35]1[CH2:36][CH2:37][N:38]([C:41](=[O:53])[C@@H:42]([NH:52][C:20]([C:10]2[CH:9]=[C:8]([Cl:7])[N:13]=[C:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:11]=2)=[O:22])[CH2:43][CH2:44][C:45]([O:47][C:48]([CH3:50])([CH3:49])[CH3:51])=[O:46])[CH2:39][CH2:40]1)=[O:34])[CH3:31]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 574316986-Chloro-2-phenylpyrimidine-4-carboxylic acidHCID 66651766ethyl 4-[(2S)-2-amino-5-tert-butoxy-5-oxopentanoyl]piperazine-1-carboxylate

Product 1

HCID 866224044-{(S)-4-tert-butoxycarbonyl-2-[(6-chloro-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Under argon, oxalyl chloride (0.843 ml) was added to a solution of 6-chloro-2-phenyl-pyrimidine-4-carboxylic acid (1.17 g) in acetonitrile (50 ml) and it was refluxed for 3 h. The reaction mixture was cooled down to 0° C. and NEt3 (2.07 ml) was added, followed by 4-((S)-2-amino-4-tert-butoxycarbonyl-butyryl)-piperazine-1-carboxylic acid ethyl ester (1.7 g) in 10 ml acetonitrile. It was stirred at RT under argon for 1 h. Water was added and the reaction mixture was extracted with EA. The org. layers were dried (Na2SO4) and evaporated off. Purification by column chromatography (EA/Hept 1/3 to 1/2) offered 1.61 g of the desired compound.

Workup

  1. temperaturewas refluxed for 3 h
  2. extractionthe reaction mixture was extracted with EA
  3. dry with materiallayers were dried (Na2SO4)
  4. customevaporated off
  5. customPurification by column chromatography (EA/Hept 1/3 to 1/2)

Sources & evidence

ORD record
ord-c6f6c11bb87e4b81a46a07c8ce9856cb
Source dataset
uspto-grants-2011_11
Patent number
US08048881B2

Reaction notes

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