Sodium Carbonate → HCID 86696527, compound

HRID 1615928Notes

Reaction equation

HRID 1615928 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][NH:12][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:31][C:32]([F:38])([F:37])[CH2:33][C:34](Cl)=[O:35]>CCOC(C)=O.C1COCC1>[F:31][C:32]([F:38])([F:37])[CH2:33][C:34]([NH:20][NH:19][C:15]1[C:14]([C:21]([F:24])([F:22])[F:23])=[C:13]([NH: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)[CH:18]=[CH:17][N:16]=1)=[O:35]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27833433,3,3-Trifluoropropionyl chlorideHCID 86696525HCID 86696525, compound

Product 1

HCID 86696527HCID 86696527, compoundYield 79.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of N-(((1S,2S)-2-(4-fluorophenyl)cyclopropyl)methyl)-2-hydrazinyl-3-(trifluoromethyl)pyridin-4-amine (0.38 g, 1.117 mmol) in EtOAc (3 mL) and THF (3 mL) and sat'd aqueous sodium carbonate (3 mL) was stirred as 3,3,3-trifluoropropanoyl chloride (0.213 g, 1.452 mmol) was added slowly. The mixture was stirred for 10 min. The reaction was diluted with EtOAc, washed with aqueous sodium bicarbonate, dried with brine, and concentrated. The crude product was purified by silica gel chromatography using 0-100% ethyl acetate/hexane as the eluent to give 3,3,3-trifluoro-N′-(4-((((1S,2S)-2-(4-fluorophenyl)cyclopropyl)methyl)amino)-3-(trifluoromethyl)pyridin-2-yl)propanehydrazide as an off-white solid (0.4 g, 71.6% yield). 1H NMR (400 MHz, CHLOROFORM-d) d 7.87 (d, J=6.3 Hz, 1H), 7.08-6.92 (m, 4H), 6.23 (d, J=6.3 Hz, 1H), 5.35 (d, J=3.8 Hz, 1H), 3.35-3.12 (m, 4H), 1.89 (dt, J=9.1, 4.9 Hz, 1H), 1.44-1.31 (m, 1H), 1.07 (dt, J=8.4, 5.5 Hz, 1H), 0.98 (dt, J=8.9, 5.5 Hz, 1H). LCMS M+1=451.1.

Workup

  1. additionwas added slowly
  2. washwashed with aqueous sodium bicarbonate
  3. dry with materialdried with brine
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a5cea3a000ef4f82b010a88d8c97cd14
Source dataset
uspto-grants-2014_07
Patent number
US08765767B2

Reaction notes

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