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

HRID 446960Notes

Reaction equation

HRID 446960 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.[CH3:48][O:49][C:50]([CH:52]1[CH2:56][N:55]([C:57]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:58])[CH:54]2[CH2:67][CH2:68][N:69]([C:70](=[O:79])[CH:71]([NH2:78])[CH:72]3[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]3)[CH:53]12)=[O:51]>CN1C(=O)CCC1.CCOC(C)=O>[CH3:48][O:49][C:50]([CH:52]1[CH2:56][N:55]([C:57]([O:59][CH2:60][C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)=[O:58])[CH:54]2[CH2:67][CH2:68][N:69]([C:70](=[O:79])[CH:71]([NH:78][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:72]3[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]3)[CH:53]12)=[O:51]

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 672816724-(2-Amino-2-cyclohexyl-acetyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester

Product 1

HCID 672806884-{2-[2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-2-cyclohexyl-acetyl}-hexahydro-pyrrolo[3,2-b]pyrrole-1,3-dicarboxylic acid 1-benzyl ester 3-methyl esterYield 115.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of Boc-N(Me)Ala-OH (113 mg, 0.56 mmol) in NMP (4 mL) was cooled to 0° C. and treated with HATU (207 mg, 0.54 mmol) followed by DIPEA (0.15 mL, 0.87 mmol). After 10 min, 17 (245 mg, 0.55 mmol) in NMP (5 mL) was added. The reaction mixture was allowed to warm to ambient temperature overnight. The solution was diluted with EtOAc, washed successively with 1M HCl, saturated NaHCO3, dried over anhydrous Na2SO4, filtered and concentrated to afford 18 as an orange-colored oil (400 mg) which was used without further purification.

Workup

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

Sources & evidence

ORD record
ord-e00ce9d0e088452eb1453cc269e1365c
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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