Sodium Azide → 3-[2-(3-azidoanilino)-4-pyrimidinyl]-N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine

HRID 896790

Reaktionsgleichung

Reaktionsgleichung von HRID 896790
[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]5[CH:24]=[C:25]([NH2:29])[CH:26]=[CH:27][CH:28]=5)[N:17]=4)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.N([O-])=O.[Na+].[N-:42]=[N+:43]=[N-].[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.O.O.CCOCC>[N:29]([C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[NH:22][C:18]1[N:17]=[C:16]([C:15]2[C:14]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)=[N:13][N:12]3[C:7]([NH:6][CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:8][CH:9]=[CH:10][C:11]=23)[CH:21]=[CH:20][N:19]=1)=[N+:42]=[N-:43]

Komponenten

8

Edukt 4

HCID 33557Sodium Azide2×HCID 516892Sodium BicarbonateHCID 10141279N'-{[7-(cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-1,3-benzenediamineHCID 23668193Sodium Nitrite2×

Produkt 1

HCID 102795183-[2-(3-azidoanilino)-4-pyrimidinyl]-N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amineAusbeute 23 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 3283Diethyl EtherLösungsmittelHCID 21899381Acetic acid--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

The following transformation was performed in the dark. To a cold (0° C.) solution of N′-{[7-(cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-1,3-benzenediamine (16.5 mg, 0.03 mmol) in acetic acid/water (80/20, 1 mL) was added aqueous sodium nitrite (0.32 mL of a stock solution prepared by dissolving 200 mg of sodium nitrite in 25 mL water, 0.04 mmol). The resultant dark solution was stirred at 0° C. for 15 minutes. Aqueous sodium azide (0.11 mL of a stock solution prepared by dissolving 200 mg of sodium azide in 10 mL of water, 0.04 mmol) was added and the resultant solution was stirred for 1.5 hours over which time it was allowed to warm to room temperature. Ether was added and the solution made basic by dropwise addition of saturated aqueous sodium bicarbonate. The organic layer was washed with brine. The aqueous layer was extracted with ethyl acetate and the combined organics were dried over magnesium sulfate. Filtration and concentration gave a solid residue which was purified by flash chromatography (4:1 to 2:1 hexanes-ethyl acetate) to provide 3-[2-(3-azidoanilino)-4-pyrimidinyl]-N-cyclopentyl-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-7-amine (4 mg, 23%) as a tinted solid. 1H NMR (CDCl3): δ 8.12 (d, 1 H), 7.71 (d, 1 H), 7.60-7.56 (m, 3 H), 7.33-7.25 (m, 3 H), 6.98 (d, 2H), 6.70 (d, 1 H), 6.54 (d, 1 H), 6.05-6.04 (m, 2 H), 4.00 (m, 1 H), 3.87 (s, 3 H), 2.13 (m, 2 H), 1.85-1.58 (m, 6 H); MS m/z 518 (M+1).

Aufarbeitung

  1. additionwas added
  2. temperatureto warm to room temperature
  3. washThe organic layer was washed with brine
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organics were dried over magnesium sulfate
  6. filtrationFiltration and concentration
  7. customgave a solid residue which
  8. customwas purified by flash chromatography (4:1 to 2:1 hexanes-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-cb46d31ddeaf40d29c64c6639034dc0b
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919352B2

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