Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 419980Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419980
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][C:11]([OH:13])=O)[C:6]=2[C:14]=1[F:15].Cl.[NH2:17][CH:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:30])([CH3:29])[C:27]#[N:28])=[CH:22][CH:21]=1)[CH3:19].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:27]([C:26]([C:23]1[CH:22]=[CH:21][C:20]([CH:18]([NH:17][C:11](=[O:13])[CH2:10][N:7]2[C:6]3[C:14]([F:15])=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH3:19])=[CH:25][CH:24]=1)([CH3:30])[CH3:29])#[N:28]

Komponenten

6

Edukt 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57939018HCID 57939018, VerbindungHCID 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

Produkt 1

HCID 24850276N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide is synthesized according to example 1 by mixing (6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (500 mg, 2.36 mmol) prepared according to scheme 2, 2-[4-(1-aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride (525 mg, 2.36 mmol) prepared according to scheme 6, DMAP (570 mg, 4.71 mmol) and HATU (896 mg, 2.36 mmol) in DMF (10.0 mL). The product is purified on HPLCMS: Waters prep LCMS, 27 ml/min, Column: SynerSi (4μ) Polar RP, 21.2×50 mm, Mobile phase: A=water (0.05% TFA) B=MeCN, Gradient used 40% to 60% B in A, in 10 min. The fractions are combined, NaOH 1 N is added and the desired compound is extracted with ethyl acetate. The combined organic fractions are concentrated under reduced pressure to yield the product (450 mg, 2.36 mmol, 50%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.49 (d, J=7.03 Hz, 3H) 1.68 (s, 6H) 5.03 (m, 1H) 5.20 (m, 2H) 7.30 (dt, J=11.23, 8.98, 7.32 Hz, 1H) 7.35-7.42 (m, 2H) 7.44-7.54 (m, 3H) 8.56 (s, 1H) MS [M+H], calcd: 383.2. found: 383.3.

Aufarbeitung

  1. customprepared
  2. customprepared
  3. customThe product is purified on HPLCMS
  4. additionNaOH 1 N is added
  5. extractionthe desired compound is extracted with ethyl acetate
  6. concentrationThe combined organic fractions are concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-d7b210fb896348dd86011e2bf174315e
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093402B2

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