Water → N-{4-[5-chloro-7-(ethylsulfanyl)-2-(4-fluorophenyl)pyrazolo[1,5-alpha]pyridin-3-yl]-2-pyrimidinyl}-N-phenylamine

HRID 896788Notes

Reaction equation

HRID 896788 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:12]=3)=[C:4]2[CH:3]=1.C([Li])CCC.[CH2:36]([S:38]SCC)[CH3:37].O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([S:38][CH2:36][CH3:37])[N:5]2[N:8]=[C:9]([C:24]3[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=3)[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:12]=3)=[C:4]2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8077Diethyl disulfideHCID 112470274-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-phenyl-2-pyrimidinamineHCID 178418339Butyllithium

Product 1

HCID 10299224N-{4-[5-chloro-7-(ethylsulfanyl)-2-(4-fluorophenyl)pyrazolo[1,5-alpha]pyridin-3-yl]-2-pyrimidinyl}-N-phenylamineYield 22.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-phenyl-2-pyrimidinamine (80 mg, 0.19 mmol) in tetrahydrofuran (5 mL) was added n-butyllithium (0.43 mL of 1.6M solution in hexane, 0.67 mmol) at −78° C. The resulting dark solution was stirred for 10 minutes, then quenched by the addition of ethyl disulfide (0.08 mL, 6.5 mmol). The reaction mixture was allowed to warm to room temperature, then water and ethyl acetate were added. The phases were separated and the ethyl acetate phase was washed with water, dried (magnesium sulfate), filtered and concentrated. The resulting residue was crystallized from acetonitrile to give N{4-[5-chloro-7-(ethylsulfanyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-N-phenylamine (20 mg, 22%) as a solid. 1H NMR (CDCl3): δ 8.30 (d, 1H), 8.22 (d, 1H), 7.66 (m, 3H), 7.40 (t, 2H), 7.1-7.24 (m, 4H), 6.75 (d, 1H), 6.52 (d, 1H), 3.20 (q, 2H), 1.54 (t, 3H); 19F-NMR (CDCl3): δ −112.55; MS m/z 476 (M+1).

Workup

  1. customThe phases were separated
  2. washthe ethyl acetate phase was washed with water
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-6f19e6e3658e4f2584325906ddc17bac
Source dataset
uspto-grants-2005_07
Patent number
US06919352B2

Reaction notes

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