Formate → N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(2-hydroxypropan-2-yl)benzamide

HRID 1055758Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055758
C[C:2]1[C:8]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[CH:11]=[CH:10]2)=[C:7]([CH3:23])[CH:6]=[CH:5][C:3]=1[NH2:4].[OH:24][C:25]([C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31](O)=[O:32])([CH3:27])[CH3:26].[CH3:37]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].C([O-])=O>CN(C=O)C.C(#N)C.CO>[CH3:37][C:5]1[CH:6]=[C:7]([CH3:23])[C:8]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[CH:11]=[CH:10]2)=[CH:2][C:3]=1[NH:4][C:31](=[O:32])[C:30]1[CH:34]=[CH:35][CH:36]=[C:28]([C:25]([OH:24])([CH3:27])[CH3:26])[CH:29]=1

Komponenten

10

Edukt 6

HCID 283FormateHCID 769Bicarbonate IonHCID 81531DiisopropylethylamineHCID 81671183-(1-Hydroxy-1-methylethyl)-benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89699939HCID 89699939, Verbindung

Produkt 1

HCID 89699666N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(2-hydroxypropan-2-yl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

250 mg (0.824 mmol) of the compound of Example 11A and 156 mg (0.865 mmol) of the compound of Example 92A were dissolved in 6.3 ml of DMF, and 376 mg (0.989 mmol) of HATU and 215 μl (1.24 mmol) of N,N-diisopropylethylamine were added in succession. After about 16 h of stirring at RT, the reaction mixture was diluted with about 3 ml of acetonitrile and then, in three portions, separated into its components by preparative HPLC (Method 36). After pooling and evaporation of the product fractions, the residue obtained was dissolved in a small amount of methanol and passed through a bicarbonate cartridge (from Polymerlabs, Stratospheres SPE, PL-HCO3 MP SPE, capacity 0.9 mmol) to prepare the free base from the formate salt from HPLC purification. Since the product obtained in this manner was still impure, it was purified further by MPLC (about 15 g of silica gel, mobile phase: cyclohexane/ethyl acetate/methanol 50:50:0→0:100:0→0:91:9). Evaporation of the product fractions and drying of the residue under high vacuum gave 238 mg (58% of theory, 95% pure) of the title compound.

Aufarbeitung

  1. customin three portions, separated into its components by preparative HPLC (Method 36)
  2. customevaporation of the product fractions
  3. customthe residue obtained
  4. customfrom HPLC purification
  5. customSince the product obtained in this manner
  6. customit was purified further by MPLC (about 15 g of silica gel, mobile phase: cyclohexane/ethyl acetate/methanol 50:50:0→0:100:0→0:91:9)
  7. customEvaporation of the product fractions
  8. customdrying of the residue under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-1cbb60f8284847ad89410dba93b41378
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394309B2

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