反応 #162010

ord-133e788c8ee241ce9fa0507ac67c9604

反応方程式

O=C(O)CCCCCCN1C(=O)C=CC1=O
7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoic acid
CCN(C(C)C)C(C)C
Hunig's base
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC)C(C)C.O=C(O)C(F)(F)F
Compound #115
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC)C(C)C.O=C(O)C(F)(F)F
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-trifluoroacetic acid salt
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
→
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)N(C)C(=O)CCCCCCN1C(=O)C=CC1=O)C(C)C
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

反応物

O=C(O)CCCCCCN1C(=O)C=CC1=O
7-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)heptanoic acid
CCN(C(C)C)C(C)C
Hunig's base
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC)C(C)C.O=C(O)C(F)(F)F
Compound #115
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)C(C)(C)NC)C(C)C.O=C(O)C(F)(F)F
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-trifluoroacetic acid salt
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU

試薬

なし

溶媒

CN(C)C=O
DMF
ClCCl
dichloromethane
CN(C)C=O
DMF
ClCCl
dichloromethane

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他Reaction
  2. 2
    その他Reaction
  3. 3
    濃縮is concentrated down and
  4. 4
    その他purification

実験手順

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).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08828401B2uspto-grants-2014_09