Diisopropylethylamine → (S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)carbamoyl)nicotinic Acid

HRID 509365

Reaktionsgleichung

Reaktionsgleichung von HRID 509365
C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=1)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[F:48][C:49]1[C:50]([C@H:55]([C:57]2[CH:62]=[CH:61][C:60]([C:63]([F:66])([F:65])[F:64])=[CH:59][CH:58]=2)[NH2:56])=[N:51][CH:52]=[CH:53][CH:54]=1.Cl.FC(F)(F)C1C=CC([C@@H](C2C(C(F)(F)F)=CC=CN=2)N)=CC=1>C(Cl)Cl>[F:48][C:49]1[C:50]([C@@H:55]([NH:56][C:11]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([OH:2])=[O:4])=[CH:10][N:9]=2)=[O:13])[C:57]2[CH:62]=[CH:61][C:60]([C:63]([F:66])([F:64])[F:65])=[CH:59][CH:58]=2)=[N:51][CH:52]=[CH:53][CH:54]=1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 3149925-(Methoxycarbonyl)pyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71144279(S)-(3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine HydrochlorideHCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine Hydrochloride

Produkt 1

HCID 71144036(S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)-methyl)carbamoyl)nicotinic Acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 5-(methoxycarbonyl)picolinic acid (101 mg, 0.558 mmol) in DCM (4 mL) was added HATU (217 mg, 0.571 mmol) and DIPEA (0.20 mL, 1.148 mmol). After stirring for 30 min at rt, the reaction was treated with (S)-(3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine hydrochloride (Intermediate 2) (125 mg, 0.364 mmol). After 16 h, the reaction was concentrated in vacuo and then taken up in THF (3 mL), MeOH (1 mL), and 1M LiOH (1 mL). The resulting mixture was stirred at rt for 2 h. The reaction mixture was concentrated in vacuo, acidified with 1N HCl and extracted with EtOAc (3×5 mL). The combined EtOAc layers were concentrated in vacuo and chromatographed through a Redi-Sep® pre-packed silica gel column (4 g), eluting with 0% to 100% EtOAc in hexane, to provide the title compound as an off-white solid. 1H NMR (CDCl3: CD3OD, 300 MHz) δ ppm 9.21 (d, J=1.5 Hz, 1H), 8.47 (d, J=4.7 Hz, 1H), 8.39 (dd, J=8.0, 1.9 Hz, 1H), 8.14 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.6 Hz, 2H), 7.42 (t, J=9.5 Hz, 1H), 7.27-7.32 (m, 1H), 6.63 (s, 1H). MS (ESI pos. ion) m/z: 419.9 (M+H).

Aufarbeitung

  1. waitAfter 16 h
  2. concentrationthe reaction was concentrated in vacuo
  3. stirringThe resulting mixture was stirred at rt for 2 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. extractionextracted with EtOAc (3×5 mL)
  6. concentrationThe combined EtOAc layers were concentrated in vacuo
  7. customchromatographed through a Redi-Sep® pre-packed silica gel column (4 g)
  8. washeluting with 0% to 100% EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-4a70336f844d40399c0d1505b2d88d1b
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096527B2

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