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

HRID 446992Notes

Reaction equation

HRID 446992 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.CN1CCOCC1.[CH2:46]([O:53][C:54](=[O:88])[NH:55][CH2:56][C:57]([N:59]1[CH2:63][CH:62]([C:64](=[O:76])[NH:65][C:66]2[C:75]3[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=3)[CH:69]=[CH:68][CH:67]=2)[CH:61]2[N:77]([C:80](=[O:87])[CH:81]([NH2:86])[C:82]([CH3:85])([CH3:84])[CH3:83])[CH2:78][CH2:79][CH:60]12)=[O:58])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN1C(=O)CCC1.CCOC(C)=O>[C:4]([O:3][C:1](=[O:2])[N:8]([CH:9]([C:11](=[O:13])[NH:86][CH:81]([C:80]([N:77]1[CH2:78][CH2:79][CH:60]2[N:59]([C:57](=[O:58])[CH2:56][NH:55][C:54]([O:53][CH2:46][C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)=[O:88])[CH2:63][CH:62]([C:64](=[O:76])[NH:65][C:66]3[C:75]4[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=4)[CH:69]=[CH:68][CH:67]=3)[CH:61]12)=[O:87])[C:82]([CH3:83])([CH3:84])[CH3:85])[CH3:10])[CH3:14])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 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 67281524{2-[4-(2-Amino-3,3-dimethyl-butyryl)-3-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid benzyl ester

Product 1

HCID 67280489(1-{1-[4-(2-Benzyloxycarbonylamino-acetyl)-6-(naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl esterYield 75.4%

Reagents, catalysts & solvents 2

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

Procedure

A solution of Boc-N(Me)Ala-OH (152 mg, 0.74 mmol) in NMP (3 mL) was cooled to 0° C. and treated with HATU (313 mg, 0.83 mmol) followed by NMM (0.15 mL). After 10 min, 58 (450 mg) 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 59 as a white solid (430 mg). Mass spectrum, m/z [771.3] (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-705fc7da378d4c409629acba91c2fa72
Source dataset
uspto-grants-2013_07
Patent number
US08481495B2

Reaction notes

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