Hydrochloric Acid → N-[5-{3-[2-({3-[(dimethylamino)methyl]phenyl}amino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}-2-(methyloxy)phenyl]-2,6-difluorobenzamide

HRID 1160006

Reaktionsgleichung

Reaktionsgleichung von HRID 1160006
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([NH:23][C:24](=[O:33])[C:25]4[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=4[F:32])[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:36][N:37]([CH2:39][C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43])[CH3:38].Cl>O1CCOCC1.CC(O)C>[CH3:38][N:37]([CH2:39][C:40]1[CH:41]=[C:42]([NH:43][C:2]2[N:7]=[C:6]([C:8]3[C:9]([C:17]4[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([NH:23][C:24](=[O:33])[C:25]5[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=5[F:32])[CH:22]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)[CH:5]=[CH:4][N:3]=2)[CH:44]=[CH:45][CH:46]=1)[CH3:36]

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 992943-amino-N,N-dimethylbenzylamineHCID 59513745N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzamide

Produkt 1

HCID 59513789N-[5-{3-[2-({3-[(dimethylamino)methyl]phenyl}amino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-2-yl}-2-(methyloxy)phenyl]-2,6-difluorobenzamideAusbeute 35,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,6-difluorobenzamide (30 mg, 0.06 mmol) in 1,4-dioxane (6 mL) and 2-propanol (3 mL) was added 3-[(dimethylamino)methyl]aniline (27 mg, 0.18 mmol) followed by 4M HCl in dioxane (0.076 ml, 0.31 mmol). After heating overnight at 80° C., the reaction was quenched with saturated NaHCO3 (25 mL), solvent removed by rotary evaporation, the aqueous layer extracted with DCM (25 mL), organic layer concentrated, and purified by column chromatography (5-50% EtOAc in hexanes) to provide the product (12.8 mg, 35%) as an off-white solid. ESIMS (M+H)+=606. 1H NMR (400 MHz, DMSO-d6) δ 2.12 (s, 6H), 3.33 (bs, 2H), 3.86 (s, 3H), 6.57 (d, 1H, J=5.49 Hz), 6.85 (d, 1H, J=7.14 Hz), 7.07-7.10 (t, J=6.78 Hz, 1H), 7.15-7.19 (m, 4H), 7.35-7.38 (m, 1H), 7.41-7.45 (m, 1H), 7.50-7.54 (m, 1H), 7.63 (d, 1H, J=6.78 Hz), 7.69 (s, 1H), 8.23 (d, 1H, J=5.49 Hz), 8.32 (s, 1H), 8.49-8.50 (m, 1H), 8.80-8.82 (m, 1H), 9.50 (s, 1H), 10.19 (s, 1H).

Aufarbeitung

  1. customthe reaction was quenched with saturated NaHCO3 (25 mL), solvent
  2. customremoved by rotary evaporation
  3. extractionthe aqueous layer extracted with DCM (25 mL), organic layer
  4. concentrationconcentrated
  5. custompurified by column chromatography (5-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-9f6557a0667d4265965f4a2bb40325ee
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812022B2

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