Methyl iodide → HCID 9901062, compound

HRID 2214920Notes

Reaction equation

HRID 2214920 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.[CH:23]([N-]C(C)C)(C)C.[Li+].CI.CCCCCC.C(OCC)(=O)C>O1CCCC1.CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.C(OCC)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([CH3:23])[N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 9879081HCID 9879081, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 9901062HCID 9901062, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

A solution of 2-(4-fluorophenyl)-3-(4-pyrimidinyl)-pyrazolo[1,5-a]pyridine (Example 1, 0.2 g, 0.69 mmol) in dry tetrahydrofuran (5 mL) was cooled to −78° C. under nitrogen and lithium diisopropylamide (0.45 mL of a 2M solution in heptane/tetrahydrofuran/ethylbenzene, 0.9 mmol) was added dropwise. The reaction mixture was stirred for about 10 minutes and methyl iodide (0.2 mL, 4 mmol) was added. The solution was allowed to warm to room temperature and stirred for a further 1.5 hours. The reaction mixture was diluted with diethyl ether (20 mL), water (20 mL) added, and the organic phase separated. The aqueous phase was further extracted with ether (20 mL) and the combined ether phases were dried over anhydrous magnesium sulfate, filtered and the solvents evaporated to give a yellow solid. Chromatography on silica gel eluting with 9:1 hexane/ethyl acetate gave the title compound, 0.080 g (38%). 1H NMR (DMSO-d6): δ 2.72 (s, 3H), 7.05 (d, J=6.3 Hz, 2H), 7.32 (t, J=8.8 Hz, 2H), 7.46 (dd, J=7.0, 8.6 Hz, 1H), 7.61 (dd, J=5.5, 8.6 Hz, 2H), 8.32 (d, J=9.0 Hz, 1H), 8.52 (d, J=5.5 Hz, 1H), 9.15 (s, 1H); APESI+MS m/z 305 (M+1)−.

Workup

  1. stirringstirred for a further 1.5 hours
  2. additionadded
  3. customthe organic phase separated
  4. extractionThe aqueous phase was further extracted with ether (20 mL)
  5. dry with materialthe combined ether phases were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customthe solvents evaporated
  8. customto give a yellow solid

Sources & evidence

ORD record
ord-de5660a61cf44cb789c5f38192ee41ab
Source dataset
uspto-grants-2006_09
Patent number
US07109209B2

Reaction notes

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