Isobutyryl chloride → N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramide

HRID 1888575Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1888575
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28](Cl)(=[O:32])[CH:29]([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH:25][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

8

Edukt 4

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504, Verbindung

Produkt 1

HCID 67203131N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramideAusbeute 12,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (80.9 mg, 0.226 mmol) in DCM (1.8 mL) was treated with isobutyryl chloride (26.3 μL, 0.249 mmol) and DIPEA (118 μL, 0.679 mmol). The reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in DCM/methanol, absorbed onto celite, and purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid (12 mg, 12%). 1H NMR (DMSO-D6, 400 MHz): 12.03 (s, 1H), 10.32 (s, 1H), 8.95 (d, J=2.2 Hz, 1H), 8.90-8.85 (m, 2H), 8.62 (s, 1H), 7.79 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.48 (s, 2H), 2.79 (dt, J=6.7, 13.5 Hz, 1H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.14 (d, J=6.8 Hz, 6H). LCMS (Method D): RT=7.73 min, M+H+=428.

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aqueous phase extracted into 20% MeOH in DCM
  3. dry with materialthe combined organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resultant residue was dissolved in DCM/methanol
  6. customabsorbed onto celite
  7. custompurified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid)

Quellen und Nachweise

ORD-Eintrag
ord-0fa2e5f291cc4a53b408ed18300d9144
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501765B2

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