Water → HCID 10276778, compound

HRID 1797060Notes

Reaction equation

HRID 1797060 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)[N:12]=3)=[C:4]2[CH:3]=1.C([Li])CCC.[CH2:35]([S:37]SCC)[CH3:36].O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:37][CH2:35][CH3:36])[N:5]2[N:8]=[C:9]([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][CH:18]4[CH2:19][CH2:20][CH2:21][CH2:22]4)[N:12]=3)=[C:4]2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8077Diethyl disulfideHCID 102231334-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamineHCID 178418339Butyllithium

Product 1

HCID 10276778HCID 10276778, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (150 mg, 0.37 mmol) in anhydrous tetrahydrofuran (5 mL) at −78° C. was added n-butyllithium (0.7 mL, 1.1 mmol of 1.6 M solution in hexane). The resulting solution was stirred for 10 minutes at −78° C., followed by addition of diethyldisulfide (0.14 mL, 1.1 mmol). The reaction was stirred at −78° C. for 20 minutes and then allowed to warm to room temperature. Water and ethyl acetate were added to the reaction mixture. The phases were separated, the aqueous phase washed with ethyl acetate and the combined organic phase dried (magnesium sulfate), filtered and concentrated in vacuo. The resulting solid was purified by flash chromatography (1:1 ethyl acetate-hexane) to give, after recrystallization from ethyl acetate N-{4-[5-chloro-7-(ethylsulfanyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine (90 mg, 52%) as a solid. 1H-NMR (CDCl3): δ 8.42(broad s, 1H), 8.08 (d, 1H), 7.66 (q, 2H), 7.17 (t, 2H), 6.73 (d, 1H), 6.31 (d, 1H), 5.18 (d, 1H), 4.20 (m, 1H), 3.22 (q, 2H), 2.0–2.1 (m, 2H), 1.4–1.9 (m, 9H); 19F-NMR (CDCl3): δ 112.8; MS m/z 468 (M+1).

Workup

  1. stirringThe reaction was stirred at −78° C. for 20 minutes
  2. temperatureto warm to room temperature
  3. customThe phases were separated
  4. washthe aqueous phase washed with ethyl acetate
  5. dry with materialthe combined organic phase dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting solid was purified by flash chromatography (1:1 ethyl acetate-hexane)
  9. customto give
  10. customafter recrystallization from ethyl acetate N-{4-[5-chloro-7-(ethylsulfanyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine (90 mg, 52%) as a solid

Sources & evidence

ORD record
ord-74cb1128f04341aab8ee8aa2da70e0bb
Source dataset
uspto-grants-2006_04
Patent number
US07034030B2

Reaction notes

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