4-Methylmorpholine → {1-[4-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester

HRID 446990Notes

Reaction equation

HRID 446990 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[C:3]([CH3:6])([CH3:5])[CH3:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH2:48]([O:55][C:56](=[O:82])[NH:57][CH2:58][C:59]([N:61]1[CH2:65][CH:64]([C:66](=[O:78])[NH:67][C:68]2[C:77]3[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=3)[CH:71]=[CH:70][CH:69]=2)[CH:63]2[NH:79][CH2:80][CH2:81][CH:62]12)=[O:60])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>CN1C(=O)CCC1.CCOC(C)=O>[C:13]([O:12][C:10](=[O:11])[NH:1][CH:2]([C:7]([N:79]1[CH2:80][CH2:81][CH:62]2[N:61]([C:59](=[O:60])[CH2:58][NH:57][C:56]([O:55][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:82])[CH2:65][CH:64]([C:66](=[O:78])[NH:67][C:68]3[C:77]4[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=4)[CH:71]=[CH:70][CH:69]=3)[CH:63]12)=[O:9])[C:3]([CH3:4])([CH3:5])[CH3:6])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67280980{2-[3-(Naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid benzyl ester

Product 1

HCID 67282206{1-[4-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl esterYield 109.4%

Reagents, catalysts & solvents 2

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

Procedure

A solution of Boc-Tle-OH (176 mg, 0.76 mmol) in NMP (3 mL) was cooled to 0° C. and treated with HATU (318 mg, 0.83 mmol) followed by NMM (0.15 mL). After 10 min, 56 (360 mg, 0.76 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 to afford 57 (570 mg) which was used without further purification. Mass spectrum, m/z [686.4] (M+H)+.

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-db4fd30ef2a846c5999572eecb79810b
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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