trans-2-Phenyl-1-cyclopropanecarbonyl chloride → trans benzyl 4-[4-amino-3-(3-methoxy-4-{[(2-phenylcyclopropyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate

HRID 432517

Reaktionsgleichung

Reaktionsgleichung von HRID 432517
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])[CH2:22][CH2:21]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12.[C:36]1([C@@H:42]2[CH2:44][C@H:43]2[C:45](Cl)=[O:46])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>N1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)=[O:27])[CH2:22][CH2:21]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:45]([C@@H:43]4[CH2:44][C@H:42]4[C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[O:46])=[C:13]([O:18][CH3:19])[CH:12]=3)[C:3]=12

Komponenten

4

Edukt 2

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chlorideHCID 22346984benzyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate

Produkt 1

HCID 131724256trans benzyl 4-[4-amino-3-(3-methoxy-4-{[(2-phenylcyclopropyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylateAusbeute 95,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
-5 °C

Versuchsvorschrift

To a mixture of benzyl 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (3.0 g, 0.0063 mol) in pyridine (100 mL) was added racemic trans-2-phenyl-cyclopropane carbonyl chloride (1.163 g, 0.007 mol) at −5° C. The mixture was stirred at −5° C. for 10 minutes then warmed up to room temperature and stirred for 1.5 hours. The mixture was quenched with an aqueous 1N solution of sodium hydroxide. Organic solvents were removed under reduced pressure. The residue was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic layer was washed with a 5% aqueous solution of citric acid (3×100 mL), 1 N aqueous solution of hydrochloride (3×100 mL), water, saturated aqueous solution of sodium bicarbonate, and brine, and dried over magnesium sulfate. The solvents were removed under reduced pressure to give trans benzyl 4-[4-amino-3-(3-methoxy-4-{[(2-phenylcyclopropyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinecarboxylate (3.47 g, 0.006 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 11.5 min. MS: MH+ 618.

Aufarbeitung

  1. temperaturethen warmed up to room temperature
  2. stirringstirred for 1.5 hours
  3. customThe mixture was quenched with an aqueous 1N solution of sodium hydroxide
  4. customOrganic solvents were removed under reduced pressure
  5. customThe residue was partitioned between water (200 mL) and ethyl acetate (200 mL)
  6. washThe organic layer was washed with a 5% aqueous solution of citric acid (3×100 mL), 1 N aqueous solution of hydrochloride (3×100 mL), water, saturated aqueous solution of sodium bicarbonate, and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvents were removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-5a80b63ebe7c44649bb7b2f34d2a3bcb
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06660744B1

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