反応 #162008

ord-d805b92339204ddca040bd99df5d7862

反応方程式

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](N)C(C)C
#250
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](N)C(C)C
N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl}pyrrolidin-2-yl]-2-methylpropanoyl}-L-phenylalanine
CCN(CC)CC
triethylamine
CN(C(=O)CCCCCN1C(=O)C=CC1=O)C(C)(C)C(=O)O
#249
CN(C(=O)CCCCCN1C(=O)C=CC1=O)C(C)(C)C(=O)O
N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-N,2-dimethylalanine
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)CCCCCN1C(=O)C=CC1=O)C(C)C
N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-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

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](N)C(C)C
#250
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](N)C(C)C
N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl}pyrrolidin-2-yl]-2-methylpropanoyl}-L-phenylalanine
CCN(CC)CC
triethylamine
CN(C(=O)CCCCCN1C(=O)C=CC1=O)C(C)(C)C(=O)O
#249
CN(C(=O)CCCCCN1C(=O)C=CC1=O)C(C)(C)C(=O)O
N-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-N,2-dimethylalanine
CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU

試薬

なし

溶媒

ClCCl
dichloromethane

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    workup.STIRRINGto stir for 3 hours
  2. 2
    その他Reaction
  3. 3
    濃縮was concentrated in vacuo
  4. 4
    その他Reverse phase purification (MethodL)
  5. 5
    その他yielded a white solid mc#120 (124 mg, 11%)
  6. 6
    その他at 45° C.

実験手順

To a stirring solution of #249 (382 mg, 1.23 mM) in 5 mL of dichloromethane, HATU (482 mg, 1.23 mM) was added followed by triethylamine (0.52 mL, 1.23 mM). The reaction was allowed to stir for 1 hour at room temperature followed by the addition of #250 (762 mg, 1.23 mM). The reaction was allowed to stir for 3 hours. Reaction was concentrated in vacuo. Reverse phase purification (MethodL) followed by lyophilization yielded a white solid mc#120 (124 mg, 11%). HPLC (Protocol A at 45° C.;) m/z 911.5 [M+H+], retention time=9.676 minutes.

出典

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