Hydrochloric Acid → 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide

HRID 1529446Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1529446
[CH3:1][N:2]([CH3:40])[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10](C1CCCCO1)[N:9]=[C:8]2[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([N:26]2[CH2:31][CH2:30][CH:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]2)[N:21]=1)=[O:4].Cl>CCOC(C)=O>[NH2:32][CH:29]1[CH2:30][CH2:31][N:26]([C:22]2[N:21]=[C:20]([C:8]3[C:7]4[C:11](=[CH:12][CH:13]=[C:5]([C:3]([N:2]([CH3:40])[CH3:1])=[O:4])[CH:6]=4)[NH:10][N:9]=3)[CH:25]=[CH:24][N:23]=2)[CH2:27][CH2:28]1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 86709796tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate

Produkt 1

HCID 679767933-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamideAusbeute 56,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.4 g, 0.728 mmol) in EtOAc (8 mL) was added HCl (4 N in dioxane, 8 mL) and the reaction was stirred at RT for 3 h The mixture was quenched with water and neutralized with NaHCO3 and extracted with EtOAc. The organic layer was separated and dried over Na2SO4, filtered and concentrated. The residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA) to give 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide (150 mg, 52%) as an off white solid. MS (ESI, pos. ion) m/z: 366.2 (M+1); 1H NMR (300 MHz, DMSO-d6): −δ 13.88 (s, 1H), 8.53 (s, 1H), 8.48 (d, 2 H, J=5.1 Hz), 7.96 (s, 3H), 7.70 (d, 1 H, J=8.6 Hz), 7.52 (dd, 1 H, J=8.6, 1.4 Hz), 7.38 (d, 1 H, J=5.1 Hz), 4.77 (d, 2 H, J=13.6 Hz), 3.41 (bs, 1H), 3.09-3.20 (m, 2H), 3.03 (s, 6H), 2.03 (d, 2 H, J=10.5 Hz), 1.47-1.58 (m, 2H).

Aufarbeitung

  1. customwas quenched with water and neutralized with NaHCO3
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-52a59c7361604ea6851f837386fdeab4
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090593B2

Notizen zur Reaktion

Wird geladen…