Diisopropylethylamine → (S)-N2-((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methyl)pyridine-2,5-dicarboxamide

HRID 2370805

Reaktionsgleichung

Reaktionsgleichung von HRID 2370805
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].CCN(C(C)C)C(C)C.CN(C([O:28]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:46][C:47]1[C:48]([C@H:53]([C:55]2[CH:60]=[CH:59][C:58]([C:61]([F:64])([F:63])[F:62])=[CH:57][CH:56]=2)[NH2:54])=[N:49][CH:50]=[CH:51][CH:52]=1.Cl.FC(F)(F)C1C=CC([C@@H](C2C(C(F)(F)F)=CC=CN=2)N)=CC=1>C(Cl)Cl.O>[F:46][C:47]1[C:48]([C@H:53]([C:55]2[CH:60]=[CH:59][C:58]([C:61]([F:63])([F:64])[F:62])=[CH:57][CH:56]=2)[NH:54][C:9]([C:6]2[CH:5]=[CH:4][C:3]([C:1]([NH2:2])=[O:28])=[CH:8][N:7]=2)=[O:11])=[N:49][CH:50]=[CH:51][CH:52]=1

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 124007345-Cyanopyridine-2-carboxylic acidHCID 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 71144005(S)-N2-((3-Fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methyl)pyridine-2,5-dicarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 5-cyanopicolinic acid (93 mg, 0.628 mmol) in DCM (6 mL) were added DIPEA (0.3 mL, 1.722 mmol) and HATU (247 mg, 0.650 mmol). The solution was stirred at rt. After 20 minutes, the reaction was treated with (S)-(3-fluoropyridin-2-yl)(4-(trifluoromethyl)phenyl)methanamine hydrochloride (Intermediate 2) (115 mg, 0.426 mmol). After stirring for 16 h, the reaction was poured into H2O (20 mL). The aqueous layer was back-extracted with DCM (10 mL). The combined DCM layers were concentrated in vacuo and taken up in 3 mL of concentrated sulfuric acid. The mixture was stirred at rt for 4 hours and then was poured into 75 g of ice. After stirring for 1 hour, the reaction was filtered, and the solids were rinsed with H2O. The solids were then taken up in EtOAc (30 mL) and washed with saturated aqueous NaHCO3. The EtOAc layer was concentrated in vacuo to give the title compound as an off-white solid. 1H NMR (CDCl3, 300 MHz) δ ppm 9.93 (d, J=7.5 Hz, 1H), 9.07 (s, 1H), 8.53 (d, J=4.7 Hz, 1H), 8.23-8.27 (m, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.55 (d, J=8.3 Hz, 2H), 7.42 (td, J=8.2, 1.3 Hz, 1H), 7.27-7.35 (m, 1H), 6.69 (dd, J=7.8, 1.9 Hz, 1H), 5.92 (br s, 2H). MS (ESI pos. ion) m/z: 419.9 (M+H).

Aufarbeitung

  1. stirringAfter stirring for 16 h
  2. extractionThe aqueous layer was back-extracted with DCM (10 mL)
  3. concentrationThe combined DCM layers were concentrated in vacuo
  4. stirringThe mixture was stirred at rt for 4 hours
  5. additionwas poured into 75 g of ice
  6. stirringAfter stirring for 1 hour
  7. filtrationthe reaction was filtered
  8. washthe solids were rinsed with H2O
  9. washwashed with saturated aqueous NaHCO3
  10. concentrationThe EtOAc layer was concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-0202b653d77242eda0e60f335b5fbce7
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08710043B2

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