Iodoethane → N-ethyl-N-pyrazolo[1,5-a]pyridin-3-ylcyclopropanecarboxamide

HRID 859135Notes

Reaction equation

HRID 859135 reaction equation
[H-].[Na+].[N:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[C:5]([NH:12][C:13]([CH:15]2[CH2:17][CH2:16]2)=[O:14])[CH:4]=1.I[CH2:19][CH3:20].CCOC(C)=O>C1COCC1.[NH4+].[Cl-].O>[CH2:19]([N:12]([C:5]1[CH:4]=[N:3][N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=12)[C:13]([CH:15]1[CH2:16][CH2:17]1)=[O:14])[CH3:20]

Participants

8

Reactant 4

HCID 6340IodoethaneHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 69588964N-pyrazolo[1,5-a]pyridin-3-ylcyclopropanecarboxamide

Product 1

HCID 69588311N-ethyl-N-pyrazolo[1,5-a]pyridin-3-ylcyclopropanecarboxamideYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

To a suspension of NaH (0.23 g, 60% in mineral oil, 5.74 mmol) in THF (15.0 mL) was added a solution of N-pyrazolo[1,5-a]pyridin-3-ylcyclopropanecarboxamide (0.77 g, 3.83 mmol) in THF (5.0 mL) at room temperature, After 15 min, iodoethane (0.52 mL, 6.5 mmol) was added. The resulting mixture was stirred for 16 h and diluted with NH4Cl solution. EtOAc and H2O were added and separated. The aqueous layer was extracted with EtOAc (2×). The combined EtOAc solution was concentrated in vacuo to dryness and the residue was subjected to column chromatography (E:H=1:4). The product was recrystalized from EtOAc/hexane to give 0.61 g (70%) of colorless solid as the title compound: mp 83–86° C.; 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J=7.0 Hz, 1H), 7.95 (s, 1H), 7.47 (d, J=8.9 Hz, 1H), 7.26–7.21 (m, 1H), 6.87 (t, J=5.9 Hz, 1H), 3.77 (q, J=7.2 Hz, 2H), 1.40–1.33 (m, 1H), 1.12 (t, J=7.1 Hz, 3H), 1.00–0.96 (m, 2H), 0.59–0.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 174.4, 139.6, 136.7, 129.0, 124.7, 115.9, 114.8, 112.7, 44.4, 31.6, 13.5, 11.9, 8.2; IR (diffuse reflectance) 2970, 1639, 1476, 1444, 1417, 1375, 1340, 1261, 1221, 1111, 1084, 941, 881, 773, 762 cm−1; MS (EI) m/z 229 (M+), 230, 229, 161, 160, 146, 133, 118, 105, 78, 69; Anal. Calcd for C13H15N3O: C, 68.10; H, 6.59; N, 18.33. Found: C, 68.02; H, 6.64; N, 18.28.

Workup

  1. customseparated
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. concentrationThe combined EtOAc solution was concentrated in vacuo to dryness
  4. customThe product was recrystalized from EtOAc/hexane

Sources & evidence

ORD record
ord-8f517ec276574cba9f6d62dac1799865
Source dataset
uspto-grants-2006_12
Patent number
US07151109B2

Reaction notes

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