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Diisopropylethylamine → 4-{2-[2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

HRID 446978
Notes
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Reaction equation

HRID 446978 reaction equation
[C:1]([N:8]([CH3:14])[C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:48]([O:55][C:56]([N:58]1[CH2:62][CH:61]([C:63](=[O:71])[NH:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[CH:60]2[N:72]([C:75](=[O:84])[CH:76]([NH2:83])[CH:77]3[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78]3)[CH2:73][CH2:74][CH:59]12)=[O:57])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>CN1C(=O)CCC1.CCOCC>[CH2:48]([O:55][C:56]([N:58]1[CH2:62][CH:61]([C:63](=[O:71])[NH:64][C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=2)[CH:60]2[N:72]([C:75](=[O:84])[CH:76]([NH:83][C:11](=[O:13])[CH:9]([N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:14])[CH3:10])[CH:77]3[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78]3)[CH2:73][CH2:74][CH:59]12)=[O:57])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672809194-(2-Amino-2-cyclohexyl-acetyl)-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester

Product 1

HCID 67282203
4-{2-[2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-3-phenylcarbamoyl-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid benzyl ester
Yield 88%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of Boc-N(Me)Ala-OH (155 mg, 0.76 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (290 mg, 0.76 mmol) and DIPEA (0.15 mL, 0.87 mmol) followed in 15 min by the addition of 40 (366 mg, 0.73 mmol). The reaction mixture was allowed to warm to ambient temperature. After 18 h, the solution was diluted with Et2O, washed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated to afford 41 (443 mg) as a white foam that was used without further purification. Mass spectrum, m/z [690.8] (M+H)+.

Workup

  1. washwashed with H2O, 1M HCl, H2O, saturated aqueous NaHCO3, brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0023cd089cc64e1293d567b64d19a648
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08481495B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes