Water → 3-(2-fluoropyridin-4-yl)-2-propylpyrazolo[1,5-a]pyridine

HRID 859964Notes

Reaction equation

HRID 859964 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][N:3]=1.N12CCCN=C1CCCCC2.[I-].[NH2:25][N+:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[C:9]([CH2:10][CH2:11][CH3:12])=[N:25][N:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=23)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 2733704Pyridinium, 1-amino-, iodide (1:1)2×HCID 45090791Pyridine, 2-fluoro-4-(1-pentynyl)- (9CI)

Product 1

HCID 100609173-(2-fluoropyridin-4-yl)-2-propylpyrazolo[1,5-a]pyridineYield 75.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold (0° C.) solution of 2-fluoro-4-pent-1-ynylpyridine (650 mg, 3.98 mmol) in acetonitrile (15 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.89 mL, 5.97 mmol) and 1-aminopyridinium iodide (974 mg, 4.38 mmol). The resultant dark solution was allowed to warm to room temperature and stirred vigorously. An additional equivalent of 1,8-diazabicyclo[5.4.0]undec-7-ene and 1-aminopyridinium iodide were added after 18 and again after 36 hours. Water was added and the mixture concentrated in vacuo. The residue was partitioned between water and ether. The organic layer was washed with brine. The aqueous layer was extracted with ether and the combined organics were dried over magnesium sulfate. Filtration and concentration followed flash chromatography on silica gel (4:1 to 3:1 hexane-ethyl acetate) provided 3-(2-fluoropyridin-4-yl)-2-propylpyrazolo[1,5-a]pyridine (765 mg, 75%) as an off-white solid. 1H NMR (CDCl3) δ 8.48 (d, 1H), 8.30 (d, 1H), 7.64 (d, 1H), 7.32–7.23 (m, 2H), 7.04 (s, 1H), 6.86 (t, 1H), 2.95 (t, 2H), 1.82 (m, 2H), 1.03 (t, 3H); 19F NMR (CDCl3) δ −68.48; MS m/z 256 (M+1).

Workup

  1. concentrationthe mixture concentrated in vacuo
  2. customThe residue was partitioned between water and ether
  3. washThe organic layer was washed with brine
  4. extractionThe aqueous layer was extracted with ether
  5. dry with materialthe combined organics were dried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-4dc2e2c02aaf4d56b21b4ab57c5ba436
Source dataset
uspto-grants-2006_12
Patent number
US07153863B2

Reaction notes

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