Lithium hydroxide, monohydrate → (S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)carbamoyl)nicotinic Acid

HRID 2370793

Reaktionsgleichung

Reaktionsgleichung von HRID 2370793
[F:1][C:2]1[C:3]([C@@H:8]([NH:20][C:21]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[CH:25][N:24]=2)=[O:22])[C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.FC(F)(F)C1C=CC([C@@H](C2C(C(F)(F)F)=CC=CN=2)N)=CC=1.COOC(C1C=CC(C(O)=O)=NC=1)=O.O.[OH-].[Li+]>CC(O)=O.O.C1COCC1>[F:1][C:2]1[C:3]([C@@H:8]([NH:20][C:21]([C:23]2[CH:32]=[CH:31][C:26]([C:27]([OH:29])=[O:28])=[CH:25][N:24]=2)=[O:22])[C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:17])[F:18])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 168937Lithium hydroxide, monohydrateHCID 71144388(S)-methyl 6-(((3-fluoro-pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)carbamoyl)nicotinateHCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine HydrochlorideHCID 866879695-((Methylperoxy)carbonyl)picolinic acid

Produkt 1

HCID 71144119(S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)carbamoyl)nicotinic Acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a 150 mL round bottom flask containing (S)-methyl 6-(((3-fluoro-pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)carbamoyl)nicotinate (250 mg, 0.556 mmol) (prepared using the general coupling procedure Table 2 with Intermediate 1 and 5-((methylperoxy)carbonyl)picolinic acid) were added THF (6 mL) and H2O (2 mL). The resulting mixture was stirred at 23° C. for 2 min. At this time, lithium hydroxide monohydrate (61.8 μL, 2.23 mmol) was added and the reaction was stirred for 3 h. The bulk of the solvent was evaporated to give a foamy solid that oiled out. The residue was dissolved in AcOH (8 mL). The solution was purified by reverse phase HPLC and the product-containing fractions concentrated to give the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 9.65 (d, J=7.3 Hz, 1H), 9.21 (s, 1H), 8.61 (d, J=4.1 Hz, 1H), 8.42 (d, J=7.3 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.63-7.42 (m, 3H), 7.39 (dd, J=4.2, 8.3 Hz, 1H), 7.20 (d, J=7.9 Hz, 2H), 6.74 (d, J=6.7 Hz, 1H). MS (ESI pos. ion) m/z: 436.2 (M+H).

Aufarbeitung

  1. customprepared
  2. stirringthe reaction was stirred for 3 h
  3. customThe bulk of the solvent was evaporated
  4. customto give a foamy solid
  5. customThe solution was purified by reverse phase HPLC
  6. concentrationthe product-containing fractions concentrated

Quellen und Nachweise

ORD-Eintrag
ord-8695e64805a649fe87decc953f32a7ef
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08710043B2

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