Diisopropylethylamine → N-[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoyl]-N,2-dimethylalanyl-N-{(1S,2R)-4-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-2-methoxy-1-[(1S)-1-methylpropyl]-4-oxobutyl}-N-methyl-L-valinamide

HRID 74827Notes

Reaction equation

HRID 74827 reaction equation
[O:1]=[C:2]1[CH:6]=[CH:5][C:4](=[O:7])[N:3]1[CH2:8][CH2:9][CH2:10][C:11]([OH:13])=O.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.FC(F)(F)C(O)=O.[CH3:54][NH:55][C:56]([CH3:104])([C:58]([NH:60][C@H:61]([C:65]([N:67]([C@@H:69]([C@@H:100]([CH3:103])[CH2:101][CH3:102])[C@H:70]([O:98][CH3:99])[CH2:71][C:72]([N:74]1[CH2:78][CH2:77][CH2:76][C@H:75]1[C@H:79]([O:96][CH3:97])[C@@H:80]([CH3:95])[C:81]([NH:83][C@H:84]([C:92]([OH:94])=[O:93])[CH2:85][C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)=[O:82])=[O:73])[CH3:68])=[O:66])[CH:62]([CH3:64])[CH3:63])=[O:59])[CH3:57]>CN(C=O)C.ClCCl>[O:7]=[C:4]1[CH:5]=[CH:6][C:2](=[O:1])[N:3]1[CH2:8][CH2:9][CH2:10][C:11]([N:55]([CH3:54])[C:56]([CH3:104])([C:58]([NH:60][C@H:61]([C:65]([N:67]([C@@H:69]([C@@H:100]([CH3:103])[CH2:101][CH3:102])[C@H:70]([O:98][CH3:99])[CH2:71][C:72]([N:74]1[CH2:78][CH2:77][CH2:76][C@H:75]1[C@H:79]([O:96][CH3:97])[C@@H:80]([CH3:95])[C:81]([NH:83][C@H:84]([C:92]([OH:94])=[O:93])[CH2:85][C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)=[O:82])=[O:73])[CH3:68])=[O:66])[CH:62]([CH3:63])[CH3:64])=[O:59])[CH3:57])=[O:13]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 34049044-Maleimidobutyric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86685778N,2-dimethylalanyl-N-{(1S,2R)-4-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-2-methoxy-1-[(1S)-1-methylpropyl]-4-oxobutyl}-N-methyl-L-valinamide-trifluoroacetic acid salt

Product 1

HCID 86685784N-[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoyl]-N,2-dimethylalanyl-N-{(1S,2R)-4-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-2-methoxy-1-[(1S)-1-methylpropyl]-4-oxobutyl}-N-methyl-L-valinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A stirring solution of 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoic acid (1.2 equivalents), HATU (1.2 equivalents), and Hunig's base (3 equivalents) in DMF and dichloromethane is allowed to stir for 30 minutes. Compound #115 (1 equivalent) is then added as a solution in dichloromethane and DMF. Reaction is monitored by LC-MS. Reaction is concentrated down and purification is completed by Isco medium pressure reverse phase chromatography (Gradient: 5%-100% water in acetonitrile).

Workup

  1. customReaction
  2. customReaction
  3. concentrationis concentrated down and
  4. custompurification

Sources & evidence

ORD record
ord-ad9fe617214d4e3c9a1afa7dc5311ae0
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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