Sodium Carbonate → HCID 86696526, compound

HRID 1615926Notes

Reaction equation

HRID 1615926 reaction equation
S(Cl)(Cl)=O.[CH:5]1([CH2:8][C:9]([OH:11])=O)[CH2:7][CH2:6]1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C@H:19]2[CH2:21][C@@H:20]2[CH2:22][NH:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([NH:30][NH2:31])[C:25]=2[C:32]([F:35])([F:34])[F:33])=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CCOC(C)=O.C1COCC1>[CH:5]1([CH2:8][C:9]([NH:31][NH:30][C:26]2[C:25]([C:32]([F:33])([F:35])[F:34])=[C:24]([NH:23][CH2:22][C@H:20]3[CH2:21][C@@H:19]3[C:16]3[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=3)[CH:29]=[CH:28][N:27]=2)=[O:11])[CH2:6][CH2:7]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 138440Cyclopropaneacetic acidHCID 86696525HCID 86696525, compound

Product 1

HCID 86696526HCID 86696526, compoundYield 51.8%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of thionyl chloride (0.713 mL, 8.23 mmol) and 2-cyclopropylacetic acid (0.247 g, 2.468 mmol) in methylene chloride (10 mL) was heated to reflux for 30 min. The solution was cooled and concentrated. The residue was dissolved in EtOAc (10 mL) and added to a stirred mixture of N-(((1S,2S)-2-(4-fluorophenyl)cyclopropyl)methyl)-2-hydrazinyl-3-(trifluoromethyl)pyridin-4-amine (0.56 g, 1.646 mmol) in EtOAc (10 mL), THF (10 mL), and sat'd Na2CO3 (10 mL). The mixture was stirred for 1 h. The reaction was diluted with EtOAc. The organic layer was separated, washed with aqueous sodium bicarbonate, washed with brine, dried over MgSO4, and concentrated to give the crude product. The crude product was purified by silica gel chromatography to give 2-cyclopropyl-N′-(4-((((1S,2S)-2-(4-fluorophenyl)-cyclopropyl)methyl)amino)-3-(trifluoromethyl)pyridin-2-yl)acetohydrazide (360 mg, 49%) as a light yellow gum. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.90 (d, J=6.0 Hz, 1H), 7.74 (br. s., 1H), 7.09-6.86 (m, 4H), 6.19 (d, J=6.0 Hz, 1H), 5.40-5.16 (m, 1H), 3.34-3.09 (m, 2H), 2.29 (d, J=7.0 Hz, 3H), 1.88 (dt, J=9.1, 4.9 Hz, 2H), 1.44-1.30 (m, 1H), 1.13-1.02 (m, 2H), 1.01-0.93 (m, 1H), 0.72-0.55 (m, 2H), 0.27 (d, J=5.8 Hz, 2H). LCMS M+1=423.2.

Workup

  1. temperatureto reflux for 30 min
  2. temperatureThe solution was cooled
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in EtOAc (10 mL)
  5. customThe organic layer was separated
  6. washwashed with aqueous sodium bicarbonate
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customto give the crude product
  11. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-003315dabd0a4e76a75dad75257153c9
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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