Triethylamine → HCID 178434276, Verbindung

HRID 537194Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 537194
Cl.C([N:6]1[CH:14]=[C:13]2[C:8]([C:9](=[O:22])[NH:10][C:11]3([CH2:20][CH:19]4[NH:21][CH:16](CC4)[CH2:15]3)[CH2:12]2)=[N:7]1)(C)(C)C.[CH3:23][C:24]1[C:32]2[C:27](=[C:28]([CH3:36])[CH:29]=[C:30]([C:33]([OH:35])=O)[CH:31]=2)[NH:26][N:25]=1.C(N(CC)CC)C.[CH3:44][CH2:45][CH2:46]P1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH3:23][C:24]1[C:32]2[C:27](=[C:28]([CH3:36])[CH:29]=[C:30]([C:33]([N:21]3[CH2:16][CH2:15][C:11]4([NH:10][C:9](=[O:22])[C:8]5[N:7]([CH:45]([CH3:46])[CH3:44])[N:6]=[CH:14][C:13]=5[CH2:12]4)[CH2:20][CH2:19]3)=[O:35])[CH:31]=2)[NH:26][N:25]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 674914372'-tert-butyl-4',6'-dihydro-8-azaspiro[bicyclo[3.2.1]octane-3,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one hydrochloride2×HCID 178434277HCID 178434277, Verbindung

Produkt 1

HCID 178434276HCID 178434276, VerbindungAusbeute 25,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 1′-isopropyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(1H)-one hydrochloride salt (Intermediate 2, 430 mg, 1.3 mmol) and 3,7-dimethyl-1H-indazole-5-carboxylic acid (306 mg, 1.6 mmol) in dimethylformamide (2 mL) was added triethylamine (0.75 mL, 5.4 mmol), 4-dimethylaminopyridine (33 mg, 0.37 mmol), and 1-propanephosphonic acid cyclic anhydride (0.52 mL, 1.74 mmol, 50% solution in ethyl acetate), and the reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated in vacuo, taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered, and concentrated to a solid. The solid was purified via flash column chromatography (0-15% methanol/dichloromethane) to afford a glassy solid. The glassy solid was stirred in ethyl acetate for 16 hours and the resulting solid collected by vacuum filtration to afford the desired product as a white solid (138 mg). +ESI (M+H) 421.0; 1H NMR (400 MHz, CD3OD, δ): 7.65 (s, 1H) 7.42 (s, 1H) 7.21 (s, 1H) 5.50 (m, 1H) 3.95 (br. s., 1H) 3.50-3.62 (br. s., 3H) 2.97 (s, 2H) 2.56 (m, 6H) 1.83 (br. s., 4H) 1.44 (d, 6H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a solid
  6. customThe solid was purified via flash column chromatography (0-15% methanol/dichloromethane)
  7. customto afford a glassy solid
  8. filtrationthe resulting solid collected by vacuum filtration

Quellen und Nachweise

ORD-Eintrag
ord-15ce9741487f4c8a8eaea116690541e8
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859773B2

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