Triethylamine → 1'-(3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)-2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one

HRID 2403703Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2403703
Cl.[Br:2][C:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:12]([OH:14])=O)[CH:11]=[C:6]2[NH:5][CH:4]=1.Cl.[C:16]([N:20]1[CH:33]=[C:32]2[C:22]([C:23](=[O:34])[CH2:24][C:25]3([CH2:31]2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[N:21]1)([CH3:19])([CH3:18])[CH3:17].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)(=O)C.CN(C)C=O>[Br:2][C:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:12]([N:28]3[CH2:27][CH2:26][C:25]4([CH2:24][C:23](=[O:34])[C:22]5[C:32](=[CH:33][N:20]([C:16]([CH3:19])([CH3:18])[CH3:17])[N:21]=5)[CH2:31]4)[CH2:30][CH2:29]3)=[O:14])[CH:11]=[C:6]2[NH:5][CH:4]=1

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 573370712-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one hydrochloride saltHCID 708961403-bromo-1H-pyrrolo[3,2-b]pyridine-6-carboxylic acid hydrochloride

Produkt 1

HCID 708961201'-(3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)-2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-oneAusbeute 71 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a suspension of 3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carboxylic acid hydrochloride (2.75 g, 9.91 mmol) and 2-tert-butyl-4,6-dihydrospiro[indazole-5,4′-piperidin]-7(2H)-one hydrochloride salt (2.95 g, 9.91 mmol) in dichloromethane (30 mL) was added triethylamine (5.52 mL, 39.6 mmol). N,N-dimethylformamide (5 mL) was then added, followed by 1-hydroxybenzotriazole (1.61 g, 11.9 mmol) and 1, (3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (2.28 g, 11.9 mmol). The reaction was allowed to stir at room temperature for 60 hours. The reaction was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate and brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-10% methanol/ethyl acetate) gave the title compound (3.39 g, 71%) as a pale brown solid. +ESI (M+1+H) 486.2; 1H NMR (400 MHz, CDCl3, δ): 10.05 (br. s., 1 H), 8.57 (d, J=1.8 Hz, 1 H), 7.87 (d, J=1.8 Hz, 1 H), 7.61 (d, J=2.7 Hz, 1 H), 7.44 (s, 1 H), 3.78 (br. s., 2 H), 3.51 (br. s., 2 H), 2.81 (s, 2 H), 2.65 (s, 2 H), 1.63 (s, 13 H).

Aufarbeitung

  1. washwashed with saturated aqueous sodium bicarbonate and brine
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash column chromatography (0-10% methanol/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-4dde3c4bb6c84ede8409b522d1d911d4
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08802688B2

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