1-Hydroxybenzotriazole → 1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamide

HRID 14172

Reaktionsgleichung

Reaktionsgleichung von HRID 14172
[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][C@@H:58]([CH2:72][C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[C:75]([F:80])[CH:74]=1)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=1>C(Cl)Cl.C(N(CC)CC)C>[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[CH:10]=[C:11]([C:14]([NH:57][C@@H:58]([CH2:72][C:73]3[CH:74]=[C:75]([F:80])[CH:76]=[C:77]([F:79])[CH:78]=3)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=3)=[O:16])[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4]

Komponenten

7

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210851741-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Produkt 1

HCID 575081851-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamideAusbeute 53,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a mixture of 1-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acid (0.2 g) in methylene chloride (15 mL) was added triethylamine (0.156 g), HOBT (0.105 g), and HATU (0.293 g). The mixture was stirred at 39° C. for 10 minutes at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.293 g) was added. The mixture was stirred at 40° C. for 4 h then poured into methylene chloride (50 mL), washed with water followed by brine then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Column chromatography on silica gel (100 mL) using 5% methanol in methylene chloride as eluent to give 0.21 g of the title compound: MS (ESI+) for C34H42F2N4O4S1 m/z 640.8 (M+H).

Aufarbeitung

  1. additionwas added
  2. washwashed with water
  3. dry with materialthen dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-34564fa2bde2476ea7d73a1bc60a19c3
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

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