Trifluoroacetic acid → 2-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide

HRID 907534Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 907534
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH:10]([CH3:28])[CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.[N:43]([C:46]1[CH:51]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:49]=[C:48]([C:56]([F:59])([F:58])[F:57])[CH:47]=1)=C=O>ClCCl>[F:53][C:52]([F:54])([F:55])[C:50]1[CH:51]=[C:46]([NH:43][C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[C:19]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)=[N:18][CH:17]=[CH:16][N:15]=3)[CH:10]([CH3:28])[CH2:9]2)=[O:7])[CH:47]=[C:48]([C:56]([F:57])([F:59])[F:58])[CH:49]=1

Komponenten

6

Edukt 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 590139432-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid tert-butyl ester

Produkt 1

HCID 103472422-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amideAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2-Methyl-3′-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (103 mgs, 0.27 mmol) was dissolved in dichloromethane (1.5 mL) to which was added TFA (2.0 mL) and the mixture stirred at room temperature for 1 hr until Boc removal was complete. The reaction mixture was concentrated in vacuo and redissolved in dichloromethane (1.0 mL) to which was added triethylamine (0.2 mL, 1.43 mmol) and 1-isocyanato-3,5-bis-trifluoromethyl-benzene (0.055 ml, 0.32 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the resulting residue purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc) to give 98.9 mgs (69%) of 2-methyl-3′-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide as a white solid after lyophilization from H2O—AcCN. 1H NMR (CDCl3) 8.77 (d, 2H), 7.94 (s, 2H), 7.82 (d, 1H), 7.71 (d, 2H), 7.52 (d, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 5.62 (s, 2H), 4.60 (m, 1H), 4.01 (m, 1H), 3.97-3.86 (m, 2H), 3.52-3.45 (m, 2H), 3.34 (m, 1H), 1.26 (d, 3H) ppm. LC-MS (MH+)=541.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in dichloromethane (1.0 mL) to which
  3. stirringThe mixture was stirred at room temperature overnight
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe resulting residue purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-84f0f70147db4f8c8ef6df3eab6974a9
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08013156B2

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