Hydrogen Peroxide → N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-(4-isopropenylphenyl)pyrazolo[1,5-a]pyridin-7-amine

HRID 861120

Reaktionsgleichung

Reaktionsgleichung von HRID 861120
COB1C2CC[CH2:11][CH:4]1[CH2:5]CC2.C([Mg]Br)(C)=C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]2[C:45]([C:46]3[CH:51]=[CH:50][N:49]=[C:48]([NH:52][CH2:53][CH2:54][CH2:55][CH3:56])[N:47]=3)=[C:35]3[CH:36]=[CH:37][CH:38]=[C:39]([NH:40][CH2:41][CH2:42][CH2:43][CH3:44])[N:34]3[N:33]=2)=[CH:28][CH:27]=1.[OH-].[Na+].OO>O1CCCC1.O.CCOCC.CN(C)C=O>[CH2:41]([NH:40][C:39]1[N:34]2[N:33]=[C:32]([C:29]3[CH:30]=[CH:31][C:26]([C:4]([CH3:11])=[CH2:5])=[CH:27][CH:28]=3)[C:45]([C:46]3[CH:51]=[CH:50][N:49]=[C:48]([NH:52][CH2:53][CH2:54][CH2:55][CH3:56])[N:47]=3)=[C:35]2[CH:36]=[CH:37][CH:38]=1)[CH2:42][CH2:43][CH3:44]

Komponenten

11

Edukt 6

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 5449649-Methoxy-9-borabicyclo(3.3.1)nonaneHCID 102068202-(4-Bromophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amineHCID 178456138HCID 178456138, Verbindung

Produkt 1

HCID 10204515N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-(4-isopropenylphenyl)pyrazolo[1,5-a]pyridin-7-amineAusbeute 27,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a cold (−78° C.) solution of 9-methoxy-9-borabicyclo[3.3.1]nonane (1 mL, 1.0 M in hexane, 1.0 mmol) in tetrahydrofuran (5 mL) was added isopropenylmagnesium bromide (2.0 mL, 0.5 M in tetrahydrofuran, 1.0 mmol) dropwise. The resultant solution was stirred at −78° C. for 5 minutes, then allowed to warm to room temperature. After 1 hour, potassium phosphate (0.33 mL, 3 M aqueous, 1.0 mmol) was added followed by N,N-dimethylformamide (5 mL), 2-(4-Bromophenyl)-N-butyl-3-[2-(butylamino)-4-pyrimidinyl]pyrazolo[1,5-a]pyridin-7-amine (100 mg, 0.20 mmol), and bis(diphenylphosphinoferrocene)palladium(II) chloride dichloromethane complex (17 mg, 0.02 mmol). The resultant solution was stirred for 72 hours at room temperature. Ether was added followed by water. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (6:1 to 4:1 to 2:1 hexanes:ethyl acetate) provided impure product. This material was taken up in tetrahydrofuran, cooled to 0° C. and 1 mL each of 10% aqueous sodium hydroxide and 30% hydrogen peroxide were added. After 30 minutes, the mixture was quenched with saturated aqueous sodium thiosulfate. Aqueous workup as reported above followed by similar chromatography provided N-butyl-3-[2-(butylamino)-4-pyrimidinyl]-2-(4-isopropenylphenyl)pyrazolo[1,5-a]pyridin-7-amine (25 mg, 27%) as an oil. 1H NMR (CDCl3): δ 8.00 (d, 1 H), 7.76 (d, 1 H), 7.62 (d, 2 H), 7.54 (d, 2 H), 7.30 (m, 1 H), 6.35 (d, 1 H), 6.07 (m, 1 H), 5.99 (d, 1 H), 5.46 (s, 2 H), 5.22 (broad, 1 H), 5.14 (s,1 H), 3.47 (m, 2 H), 3.36 (m, 2 H), 2.20 (s, 3 H), 1.77–1.42 (m, 8 H), 1.00–0.95 (m 6 H); MS m/z 455 (M+1). This material was treated with anhydrous hydrochloric acid in ether to provide the corresponding hydrochloride salt.

Aufarbeitung

  1. washThe organic layer was washed with brine
  2. extractionThe aqueous layer was extracted with ether
  3. dry with materialthe combined organics dried over magnesium sulfate
  4. filtrationFiltration and concentration
  5. customprovided impure product
  6. temperaturecooled to 0° C.
  7. waitAfter 30 minutes
  8. customthe mixture was quenched with saturated aqueous sodium thiosulfate

Quellen und Nachweise

ORD-Eintrag
ord-d3722e90a11946b68c0c062d2c41a959
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07153855B2

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