Sodium hydride → 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-N-pyrazin-2-yl-propionamide

HRID 2381484Notes

Reaction equation

HRID 2381484 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][CH:14]=[CH:13][C:4]=1[O:5][C:6]1[CH:11]=[N:10][NH:9][C:8](=[O:12])[CH:7]=1.[H-].[Na+].Br[CH:22]([CH2:32][CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1)[C:23]([NH:25][C:26]1[CH:31]=[N:30][CH:29]=[CH:28][N:27]=1)=[O:24]>O1CCCC1>[CH:33]1([CH2:32][CH:22]([N:9]2[C:8](=[O:12])[CH:7]=[C:6]([O:5][C:4]3[CH:13]=[CH:14][CH:15]=[CH:16][C:3]=3[C:2]([F:17])([F:1])[F:18])[CH:11]=[N:10]2)[C:23]([NH:25][C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)=[O:24])[CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 66875509HCID 66875509, compoundHCID 68988679HCID 68988679, compound

Product 1

HCID 444645513-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-N-pyrazin-2-yl-propionamideYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one (63.8 mg, 0.24 mmol) in tetrahydrofuran (1.24 mL) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (12 mg, 0.2 mmol). The reaction stirred at 0° C. for 5 min and then at 25° C. for an additional 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-N-pyrazin-2-yl-propionamide (81.4 mg, 0.27 mmol) in a minimal amount of tetrahydrofuran. The reaction was then warmed to 50° C., where it stirred overnight. After this time, the reaction was partitioned between water (100 mL) and methylene chloride (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 12 g, 50-75% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-N-pyrazin-2-yl-propionamide (31.8 mg, 27%) as a white solid; ES+-HRMS m/e calcd for C23H22N5O3F3 [M+H+] 474.1748, found 474.1746. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.10 (m, 1H), 1.23-1.75 (m, 8H), 1.98 (m, 1H), 2.30 (m, 1H), 5.58 (dd, J=4.4, J=11.0 Hz, 1H), 5.92 (d, J=2.7 Hz, 1H), 7.48-7.63 (m, 2H), 7.81 (t, J=7.1 Hz, 1H), 7.88 (d, J=7.8 Hz, 1H), 8.20 (d, J=2.7 Hz, 1H), 8.36 (d, J=2.7 Hz, 1H), 8.41 (br.s., 1H), 9.21 (s, 1H), 11.25 (s, 1H).

Workup

  1. waitat 25° C. for an additional 30 min
  2. temperatureThe reaction was then warmed to 50° C.
  3. stirringwhere it stirred overnight
  4. customAfter this time, the reaction was partitioned between water (100 mL) and methylene chloride (2×100 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b801957e0e484d6288914454b7ee6612
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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