Methyl iodide → HCID 59294499, Verbindung

HRID 1877396

Reaktionsgleichung

Reaktionsgleichung von HRID 1877396
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.[CH2:19](N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:52]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=2[NH2:61])[CH2:54][CH2:53]1.[H-].[Na+].IC>CN(C=O)C>[CH:52]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=2[N:61]([CH3:19])[C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[N:13][C:5]=2[O:4][C:3]2[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:2]=2[Cl:1])[CH2:54][CH2:53]1

Komponenten

8

Edukt 6

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 766182-CyclopropylanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167959962-(2,5-Dichloro-phenoxy)-nicotinic acid

Produkt 1

HCID 59294499HCID 59294499, VerbindungAusbeute 20,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (42.6 mg, 0.15 mmol, 1.0 equiv; Example 31, Step 1) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (97 mg, 128 μL, 0.75 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (67 mg, 0.18 mmol, 1.2 equiv; [CAS RN 148893-10-1]) and the reaction mixture stirred at rt for 30 min. After addition of 2-cyclopropyl-phenylamine (24 mg, 0.18 mmol, 1.2 equiv; [CAS RN 3158-73-4]) the reaction mixture was heated by microwave irradiation to 100° C. After 30 min, sodium hydride (8.6 mg, 0.2 mmol, 2.0 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (28.4 mg, 12 μL, 0.2 mmol, 2.0 equiv; [CAS RN 74-88-4]) were added and stirring of the reaction mixture at rt continued for 2 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 12.6 mg (20%) of the title compound. MS (ISP): 412.9 [M+H]+.

Aufarbeitung

  1. temperaturewas heated by microwave irradiation to 100° C
  2. waitAfter 30 min
  3. stirringstirring of the reaction mixture at rt
  4. waitcontinued for 2 h
  5. customRemoval of the solvent mixture
  6. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  7. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  8. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-c54848308ccf4da1a43c1705d9b4a4f2
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309734B2

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