Water → (R)-N-(5-cyano-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-1-(4-(trifluoro-methyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 445341

Reaktionsgleichung

Reaktionsgleichung von HRID 445341
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[C:6]([CH:9]=1)[C:7]#[N:8].[H-].[Na+].[F:18][C:19]([F:49])([F:48])[C:20]1[CH:25]=[CH:24][C:23]([C@@H:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][CH2:28][N:27]2[C:36](OC2C=CC([N+]([O-])=O)=CC=2)=[O:37])=[CH:22][CH:21]=1.O>C1COCC1.CO>[C:7]([C:6]1[CH:9]=[C:2]([NH:1][C:36]([N:27]2[CH2:28][CH2:29][C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:26]2[C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:48])([F:18])[F:49])=[CH:21][CH:22]=2)=[O:37])[CH:3]=[N:4][C:5]=1[O:10][CH2:11][C:12]([F:15])([F:13])[F:14])#[N:8]

Komponenten

7

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 59536297(R)-4-Nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 609222435-Amino-2-(2,2,2-trifluoroethoxy)nicotinonitrile

Produkt 1

HCID 59536418(R)-N-(5-cyano-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-1-(4-(trifluoro-methyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 5-amino-2-(2,2,2-trifluoroethoxy)nicotinonitrile (49 mg, 226 μmol) in THF (1.0 mL) was added sodium hydride, 60% dispersion in mineral oil (26 mg, 678 μmol). The resulting mixture was then stirred at RT for 15 min. Then, (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (100 mg, 226 μmol, example 88) was added and the mixture was stirred at RT for overnight. Then, a solution of H2O and MeOH (1:1, 0.2 mL) was added and the solvents were removed. The residue was then dissolved in a solution of DMSO and MeOH (1:1, 1 mL). The solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give the desired product, which was dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP resin (polymerlabs, 200 mg/6 mL tube) and the resin was washed with MeOH (2×0.5 mL). The combined washings were then concentrated and dried under vacuum to give the title compound as a light yellow solid. MS (ESI, positive ion) m/z: 521 (M+H).

Aufarbeitung

  1. stirringthe mixture was stirred at RT for overnight
  2. customthe solvents were removed
  3. dissolutionThe residue was then dissolved in a solution of DMSO and MeOH (1:1, 1 mL)
  4. customThe solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-4597e256695e4eb494467242804f360b
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08476297B2

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