Sodium Carbonate → HCID 86696531, compound

HRID 1615931Notes

Reaction equation

HRID 1615931 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[CH2:11][N:12]([CH3:25])[C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][NH2:20])[C:14]=2[C:21]([F:24])([F:23])[F:22])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:32][C:33]([F:39])([F:38])[CH2:34][C:35](Cl)=[O:36]>CCOC(C)=O.C1COCC1>[F:32][C:33]([F:39])([F:38])[CH2:34][C:35]([NH:20][NH:19][C:15]1[C:14]([C:21]([F:24])([F:22])[F:23])=[C:13]([N:12]([CH2:11][C@@H:9]2[CH2:10][C@H:8]2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH3:25])[CH:18]=[CH:17][N:16]=1)=[O:36]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27833433,3,3-Trifluoropropionyl chlorideHCID 86696530HCID 86696530, compound

Product 1

HCID 86696531HCID 86696531, compoundYield 70.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of trans-N-((2-(4-fluorophenyl)cyclopropyl)methyl)-2-hydrazinyl-N-methyl-3-(trifluoromethyl)pyridin-4-amine (0.5 g, 1.411 mmol) in EtOAc (6 mL), THF (6 mL) and 2.0 M of aqueous sodium carbonate (3.53 mL, 7.06 mmol) was added 3,3,3-trifluoropropionyl chloride (0.248 g, 1.693 mmol) dropwise at rt. The resulting mixture was stirred at under nitrogen for 10 min. The reaction mixture was partitioned between EtOAc/aqueous sodium bicarbonate. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 mL) and brine (20 mL), dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 0-30% EtOAc/hexane as the eluent to give trans-3,3,3-trifluoro-N′-(4-(((2-(4-fluorophenyl)cyclopropyl)methyl)(methyl)amino)-3-(trifluoromethyl)pyridin-2-yl)propanehydrazide (0.46 g, 66.7% yield) as a white solid. 1H NMR (500 MHz, METHANOL-d4) δ 7.88 (d, J=6.0 Hz, 1H), 7.08-7.01 (m, 2H), 6.99-6.91 (m, 2H), 6.58 (d, J=6.1 Hz, 1H), 3.41 (dd, J=14.0, 5.6 Hz, 1H), 3.36-3.24 (m, 2H), 3.13 (dd, J=14.0, 7.6 Hz, 1H), 1.81-1.71 (m, 1H), 1.32-1.21 (m, 1H), 0.99 (dt, J=8.6, 5.2 Hz, 1H), 0.87 (dt, J=8.8, 5.4 Hz, 1H). LCMS: M+1=465.13.

Workup

  1. customThe reaction mixture was partitioned between EtOAc/aqueous sodium bicarbonate
  2. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with aqueous sodium bicarbonate (2×20 mL) and brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-df99ccc6bf4149598d03295d76826c64
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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