4-Methylmorpholine → HCID 86649123, compound

HRID 1471039Notes

Reaction equation

HRID 1471039 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:17]([CH3:19])[CH3:18])[C:7]([N:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[C:14]([OH:16])=O)=[O:8])=[O:4].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1.[Br:48][C:49]1[CH:54]=[CH:53][C:52]([CH:55]2[N:59]([C:60]3[CH:65]=[CH:64][C:63]([C:66]([CH3:69])([CH3:68])[CH3:67])=[CH:62][CH:61]=3)[CH:58]([C:70]3[CH:71]=[C:72]([NH2:88])[C:73]([NH:76][CH2:77][C:78]4[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][C:79]=4[O:86][CH3:87])=[CH:74][CH:75]=3)[CH2:57][CH2:56]2)=[CH:51][CH:50]=1>CN(C=O)C.CCOC(C)=O>[Br:48][C:49]1[CH:54]=[CH:53][C:52]([CH:55]2[N:59]([C:60]3[CH:61]=[CH:62][C:63]([C:66]([CH3:69])([CH3:68])[CH3:67])=[CH:64][CH:65]=3)[CH:58]([C:70]3[CH:75]=[CH:74][C:73]([NH:76][CH2:77][C:78]4[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][C:79]=4[O:86][CH3:87])=[C:72]([NH:88][C:14]([C@@H:10]4[CH2:11][CH2:12][CH2:13][N:9]4[C:7](=[O:8])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH:17]([CH3:19])[CH3:18])=[O:16])[CH:71]=3)[CH2:57][CH2:56]2)=[CH:51][CH:50]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 12071044(S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acidHCID 67381738HCID 67381738, compound

Product 1

HCID 86649123HCID 86649123, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

(S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid (0.339 g, 1.245 mmole) and HOBt (0.191 g, 1.245 mmole) were dissolved in DMF (4 mL) cooled in an ice bath and treated with EDAC (0.245 g, 1.245 mmole) and N-Methylmorpholine (NMM) (0.55 mL, 4.98 mmole). The resulting solution was stirred 5 minutes in the ice bath, treated dropwise with the product from Example 191F in DMF (4 mL) and the resulting dark mixture was stirred in the ice bath for 1 hr then at room temperature for 18 hr. The next day, the reaction mixture was diluted with EtOAc (50 mL) and the organic layer was washed with 10% NaHCO3 and 10% NaCl, dried over anhydrous Na2SO4(s), filtered and the solvent was removed in vacuo leaving an oily residue as the title compound as a mixture of isomers (0.65 g). ESI+(m/z): 868.2.

Workup

  1. temperaturecooled in an ice bath
  2. washthe organic layer was washed with 10% NaHCO3 and 10% NaCl
  3. dry with materialdried over anhydrous Na2SO4(s)
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-6c195184c19d49a6bccc2a4f4712605c
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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