1-Hydroxybenzotriazole → N-{4'-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1'-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide

HRID 970221Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 970221
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:21])[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH:11]=2)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]([OH:30])=O)=[CH:24][CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:74][CH2:75][CH2:76][CH2:77][N:78]1[CH:82]=[CH:81][N:80]=[CH:79]1>CN(C=O)C>[N:78]1([CH2:77][CH2:76][CH2:75][NH:74][C:28]([C:25]2[CH:24]=[CH:23][C:22]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[C:5]([NH:8][C:9](=[O:21])[C:10]4[CH:15]=[CH:14][N:13]=[C:12]([N:16]5[CH2:17][CH2:18][CH2:19][CH2:20]5)[CH:11]=4)[CH:4]=3)=[CH:27][CH:26]=2)=[O:30])[CH:82]=[CH:81][N:80]=[CH:79]1

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 787361H-Imidazole-1-propanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 113501482'-Methyl-5'-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1'-biphenyl-4-carboxylic acid

Produkt 1

HCID 69151799N-{4'-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1'-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2′-Methyl-5′-[(2-pyrrolidin-1-ylisonicotinoyl)amino]-1,1′-biphenyl-4-carboxylic acid (40 mg, 0.1 mmol), HATU (38 mg, 0.1 mmol), HOBT (13 mg, 0.1 mmol), DIPEA (52 μl), and 1-(3-aminopropyl)imidazole (15 mg, 0.12 mmol) were mixed in DMF (1 ml) and stirred at room temperature for 18 hours. The solvent was evaporated under vacuum and the residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml). The organic phase was applied to a silica gel flash column and eluted with toluene/methanol (8:2), which after evaporation of the solvents under vacuum gave N-{4′-[(3-imidazol-1-ylpropylamino)carbonyl]-6-methyl-1,1′-biphenyl-3-yl}-2-pyrrolidin-1-ylisonicotinamide (12 mg, 24%). NMR; δH [2H6]-DMSO 10.31,(1H, s), 8.60,(1H, t), 8.19,(1H, d), 7.93,(2H, d), 7.71,(1H, dd), 7.67,(2H, m), 7.45,(2H, d), 7.30,(1H, d), 7.22,(1H, s), 6.96,(1H, s), 6.86,(1H, s), 4.03,(2H, t), 3.43,(4H, m), 3.26,(2H, q), 2.20,(3H, s), 1.99-1.93,(6H, m). LCMS: retention time 2.24 min, MH+509.

Aufarbeitung

  1. customThe solvent was evaporated under vacuum
  2. customthe residue partitioned between DCM (5 ml) and aqueous sodium carbonate (1M, 5 ml)
  3. washeluted with toluene/methanol (8:2), which
  4. customafter evaporation of the solvents under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-505ea965be7c4442a689e936cd5204e6
Quelldatensatz
uspto-grants-2007_12
Patentnummer
US07309800B2

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