4-Methylmorpholine → 4-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

HRID 446988Notes

Reaction equation

HRID 446988 reaction equation
[NH:1]([C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])[CH2:2][C:3]([OH:5])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[C:47]([O:51][C:52]([N:54]1[CH2:58][CH2:57][CH:56]2[NH:59][CH2:60][CH:61]([C:62](=[O:74])[NH:63][C:64]3[C:73]4[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=4)[CH:67]=[CH:66][CH:65]=3)[CH:55]12)=[O:53])([CH3:50])([CH3:49])[CH3:48]>CN1C(=O)CCC1.CCOC(C)=O>[C:47]([O:51][C:52]([N:54]1[CH2:58][CH2:57][CH:56]2[N:59]([C:3](=[O:5])[CH2:2][NH:1][C:6]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)=[O:7])[CH2:60][CH:61]([C:62](=[O:74])[NH:63][C:64]3[C:73]4[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=4)[CH:67]=[CH:66][CH:65]=3)[CH:55]12)=[O:53])([CH3:50])([CH3:48])[CH3:49]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 14349BenzyloxycarbonylglycineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672813746-(Naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Product 1

HCID 672815284-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl esterYield 73.5%

Reagents, catalysts & solvents 2

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

Procedure

A solution of Cbz-Gly-OH (250 mg, 1.20 mmol) in NMP (2 mL) was cooled to 0° C. and treated with HATU (502 mg, 1.32 mmol) followed by NMM (0.2 mL). After 10 min, 54 (360 mg, 0.95 mmol) in NMP (2 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. Purification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 55 as a white solid (400 mg). Mass spectrum, m/z [573.2] (M+H)+.

Workup

  1. washwashed successively with 1M HCl, saturated NaHCO3
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min)

Sources & evidence

ORD record
ord-deeb4adcd93b4d3b894c69432f1cf3cf
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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