Ethylmorpholine → 3(RS)-[[N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-5,5,5-trifluoro-2',4'-dimethyl-2-oxovaleranilide

HRID 635621Notes

Reaction equation

HRID 635621 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4](S(O)(=O)=O)=[CH:3][CH:2]=1.[NH2:12][CH:13]([CH2:27][C:28]([F:31])([F:30])[F:29])[C:14](=[O:26])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][C:19]=1[CH3:25])=[O:16].[C:32]([O:36][C:37]([CH2:39][CH2:40][C:41]([NH:43][C@H:44]([C:53]([NH:55][C@H:56]([C:66]([NH:68][C@H:69]([C:78]([NH:80][C@H:81]([C:86]([NH:88][C@H:89]([C:94](O)=[O:95])[CH2:90][CH:91]([CH3:93])[CH3:92])=[O:87])[C:82]([CH3:85])([CH3:84])[CH3:83])=[O:79])CC1C=CC=CC=1C)=[O:67])[CH2:57][CH2:58][C:59](=[O:65])[O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:54])[CH2:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:42])=[O:38])([CH3:35])([CH3:34])[CH3:33].[CH3:97]N(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C>ClCCl>[C:32]([O:36][C:37]([CH2:39][CH2:40][C:41]([NH:43][C@H:44]([C:53]([NH:55][C@H:56]([C:66]([NH:68][C@H:69]([C:78]([NH:80][C@H:81]([C:86]([NH:88][C@H:89]([C:94]([NH:12][CH:13]([CH2:27][C:28]([F:29])([F:30])[F:31])[C:14](=[O:26])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][C:19]=1[CH3:25])=[O:16])=[O:95])[CH2:90][CH:91]([CH3:92])[CH3:93])=[O:87])[C:82]([CH3:85])([CH3:84])[CH3:83])=[O:79])[CH2:11][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:97])=[O:67])[CH2:57][CH2:58][C:59](=[O:65])[O:60][C:61]([CH3:63])([CH3:64])[CH3:62])=[O:54])[CH2:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:42])=[O:38])([CH3:33])([CH3:34])[CH3:35]

Participants

7

Reactant 5

HCID 7525EthylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 212588793(RS)-amino-5,5,5-trifluoro-2',4'-dimethyl-2-oxovaleranilide p-toluenesulphonateHCID 22942121N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine

Product 1

HCID 206399213(RS)-[[N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-5,5,5-trifluoro-2',4'-dimethyl-2-oxovaleranilideYield 25.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

115 mg (0.25 mmol) of the foregoing 3(RS)-amino-5,5,5-trifluoro-2′,4′-dimethyl-2-oxovaleranilide p-toluenesulphonate (1:1), 183 mg (0.2 mmol) of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine, 58 mg (0.3 mmol) of 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide, 30 mg (0.22 mmol) of 1-hydroxybenzotriazole and 46 mg (0.4 mmol) of N-ethylmorpholine were dissolved in 10 ml of dichloromethane and the solution was stirred at room temperature for 6 hours. The solution was then washed with 2M hydrochloric acid and saturated sodium hydrogen carbonate solution, dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was chromatographed on silica gel using 3.5% methanol in dichloromethane for the elution. The solid obtained was triturated with diethyl ether and filtered off to give 61 mg of 3(RS)-[[N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucyl]amino]-5,5,5-trifluoro-2′,4′-dimethyl-2-oxovaleranilide as a white solid, MS: m/e 1188.4 [M+H]+.

Workup

  1. washThe solution was then washed with 2M hydrochloric acid and saturated sodium hydrogen carbonate solution
  2. dry with materialdried over anhydrous magnesium sulphate
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was chromatographed on silica gel using 3.5% methanol in dichloromethane for the elution
  6. customThe solid obtained
  7. customwas triturated with diethyl ether
  8. filtrationfiltered off

Sources & evidence

ORD record
ord-533725e795c14e4698446f3906ea55ef
Source dataset
uspto-grants-2001_02
Patent number
US06187905B1

Reaction notes

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