N,N'-Dimethylethylenediamine → N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamide

HRID 55742Notes

Reaction equation

HRID 55742 reaction equation
CNCCNC.[Cl:7][C:8]1[C:12]([NH:13][C:14](=[O:24])[CH2:15][CH2:16][S:17][CH2:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:11][NH:10][N:9]=1.C(=O)([O-])[O-].[K+].[K+].Br[C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1>[Cu]I.C(#N)C>[Cl:7][C:8]1[C:12]([NH:13][C:14](=[O:24])[CH2:15][CH2:16][S:17][CH2:18][CH2:19][C:20]([F:21])([F:22])[F:23])=[CH:11][N:10]([C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)[N:9]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 122863-BromopyridineHCID 178520908HCID 178520908, compound

Product 1

HCID 86700584N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamideYield 53.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A 100 mL, 3-neck round bottom flask was charged with copper(I) iodide (0.343 g, 1.80 mmol), acetonitrile (50 mL), N,N′-dimethylethane-1,2-diamine (0.318 g, 3.61 mmol), N-(3-chloro-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamide (2.72 g, 9.02 mmol), potassium carbonate (2.49 g, 18.0) and 3-bromopyridine (1.71 g, 10.8 mmol). The mixture was purged with nitrogen three times and heated to 80° C. for 4 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate] indicated that only a trace of starting material remained. The mixture was filtered through a Celite® pad and the pad was rinsed with acetonitrile (20 mL). The filtrates were concentrated to dryness and the residue was purified by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent. The fractions containing pure product were concentrated to dryness and further dried under vacuum to afford a white solid (1.82 g, 53%): mp 99-102° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.05 (d, J=2.7 Hz, 1H), 8.86 (s, 1H), 8.54 (dd, J=4.5, 1.4 Hz, 1H), 8.21 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.54 (dd, J=8.4, 4.7 Hz, 1H), 2.86 (t, J=7.3 Hz, 2H), 2.74 (td, J=6.5, 5.6, 4.2 Hz, 4H), 2.59 (ddd, J=11.7, 9.7, 7.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.32, 147.49, 139.44, 135.47, 133.40, 126.60 (q, J=296 Hz), 125.49, 124.23, 122.30, 120.00, 35.18, 33.42 (q, J=27.2 Hz), 26.77, 23.05 (q, J=3.3 Hz); EIMS m/z 378 ([M]+).

Workup

  1. customThe mixture was purged with nitrogen three times
  2. filtrationThe mixture was filtered through a Celite® pad
  3. washthe pad was rinsed with acetonitrile (20 mL)
  4. concentrationThe filtrates were concentrated to dryness
  5. customthe residue was purified by flash column chromatography
  6. additionThe fractions containing pure product
  7. concentrationwere concentrated to dryness
  8. customfurther dried under vacuum

Sources & evidence

ORD record
ord-7665432342f040848b56aa1efe2d6c45
Source dataset
uspto-grants-2016_09
Patent number
US09433215B2

Reaction notes

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