Ethyl Acetate → N-{4-[2-(4-Fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl]pyridin-2-yl}propanamide

HRID 1890259Notes

Reaction equation

HRID 1890259 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22](I)=[C:17]3[CH2:18][CH2:19][CH2:20][CH2:21][N:16]3[N:15]=2)=[CH:10][CH:9]=1.CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([NH:38][C:39](=[O:42])[CH2:40][CH3:41])[CH:33]=2)O1.C(OCC)(=O)C>O1CCOCC1>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38][C:39](=[O:42])[CH2:40][CH3:41])[CH:33]=3)=[C:17]3[CH2:18][CH2:19][CH2:20][CH2:21][N:16]3[N:15]=2)=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 497605002-Propionamidopyridine-4-Boronic Acid Pinacol EsterHCID 674380732-(4-Fluorophenyl)-3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine

Product 1

HCID 67439592N-{4-[2-(4-Fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl]pyridin-2-yl}propanamideYield 79.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Under argon, 1.39 ml of a 2M aqueous Na2CO3 solution are added dropwise to a solution of 200 mg (0.55 mmol) of 2-(4-fluorophenyl)-3-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine, 168 g (0.61 mmol) of N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]propanamide in 2 ml of dioxane, and 32 mg (0.04 mmol) of Pd(PCy3)2Cl2 are added. In a microwave reactor, the reaction mixture is heated at 120° C. for 15 min. After cooling, 50 ml of ethyl acetate are added, the reaction mixture is filtered through kieselguhr and the filtrate is extracted with ethyl acetate. The combined organic phases are washed with water, dried over MgSO4 and freed from the solvent under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 159 mg (78%) of the desired product; log P(HCOOH): 1.97; 1H-NMR (MeCN-d3): 8.54 (br.s, 1H), 8.11 (d. 1H), 8.02 (s, 1H), 7.42 (dd, 2H), 7.04 (dd, 2H), 6.77 (d, 1H), 4.16 (dd, 2H), 2.81 (dd, 2H), 2.40 (q, 2H), 1.77 (m, 2H), 1.11 (t, 3H).

Workup

  1. additionare added
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture is filtered through kieselguhr
  4. extractionthe filtrate is extracted with ethyl acetate
  5. washThe combined organic phases are washed with water
  6. dry with materialdried over MgSO4
  7. customPurification by column chromatography on silica gel (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-fbb2a15f24a8477c8b0e0c4dcc3d8884
Source dataset
uspto-grants-2013_08
Patent number
US08507472B2

Reaction notes

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