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

HRID 896790

Reaction equation

HRID 896790 reaction equation
[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]

Participants

8

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 21899381Acetic acid--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-cb46d31ddeaf40d29c64c6639034dc0b
Source dataset
uspto-grants-2005_07
Patent number
US06919352B2

Linked notes

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