Diisopropylethylamine → N-[7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoyl]-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 74828Notes

Reaction equation

HRID 74828 reaction equation
[O:1]=[C:2]1[CH:6]=[CH:5][C:4](=[O:7])[N:3]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=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.[CH3:57][NH:58][C:59]([CH3:107])([C:61]([NH:63][C@H:64]([C:68]([N:70]([C@@H:72]([C@@H:103]([CH3:106])[CH2:104][CH3:105])[C@H:73]([O:101][CH3:102])[CH2:74][C:75]([N:77]1[CH2:81][CH2:80][CH2:79][C@H:78]1[C@H:82]([O:99][CH3:100])[C@@H:83]([CH3:98])[C:84]([NH:86][C@H:87]([C:95]([OH:97])=[O:96])[CH2:88][C:89]1[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=1)=[O:85])=[O:76])[CH3:71])=[O:69])[CH:65]([CH3:67])[CH3:66])=[O:62])[CH3:60]>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][CH2:11][CH2:12][CH2:13][C:14]([N:58]([CH3:57])[C:59]([CH3:107])([C:61]([NH:63][C@H:64]([C:68]([N:70]([C@@H:72]([C@@H:103]([CH3:106])[CH2:104][CH3:105])[C@H:73]([O:101][CH3:102])[CH2:74][C:75]([N:77]1[CH2:81][CH2:80][CH2:79][C@H:78]1[C@H:82]([O:99][CH3:100])[C@@H:83]([CH3:98])[C:84]([NH:86][C@H:87]([C:95]([OH:97])=[O:96])[CH2:88][C:89]1[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=1)=[O:85])=[O:76])[CH3:71])=[O:69])[CH:65]([CH3:66])[CH3:67])=[O:62])[CH3:60])=[O:16]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 105133737-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoic acidHCID 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 86685785N-[7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoyl]-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 7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoic 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-133e788c8ee241ce9fa0507ac67c9604
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

Loading…