Triethylamine → HCID 66684797, compound

HRID 1048972Notes

Reaction equation

HRID 1048972 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH3:9])[C:5]([NH2:10])=[CH:4][C:3]=1[F:11].[F:12][C:13]([F:24])([F:23])[C:14]1[C:19]([C:20](O)=[O:21])=[CH:18][N:17]=[CH:16][CH:15]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[C:3]([F:11])=[CH:4][C:5]([NH:10][C:20](=[O:21])[C:19]2[C:14]([C:13]([F:24])([F:12])[F:23])=[CH:15][CH:16]=[N:17][CH:18]=2)=[C:6]([NH:8][CH3:9])[CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27775493-Pyridinecarboxylic acid, 4-(trifluoromethyl)-HCID 89093530HCID 89093530, compound

Product 1

HCID 66684797HCID 66684797, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To the solution of compound 5-chloro-4-fluoro-N1-methylbenzene-1 2-diamine (0.3 g, 0.00172 mol) and 4-trifluoromethylnicotinic acid (0.36 g, 0.00189 mol) in DMF (5 ml) was added EDC-HCl (0.27 g, 0.00206 mol) followed by HOBt (0.39 g, 0.00206 mol) and Et3N (0.047 g, 0.00344 mol). Reaction mixture was heated at 80° C. for 12 h. Reaction mass was quenched with ice water and layers were separated. The aqueous layer was extracted with EtOAc (3×10 ml). The combined organic extracts were washed with sat NaHCO3 solution and brine dried over Na2SO4 and concentrated to get crude product which was purified by column chromatography to provide N-(4-chloro-5-fluoro-2-(methyl amino)phenyl)-4-(tri-fluoromethyl)nicotinamide as a brown colored solid. 1H NMR (400 MHz, DMSO-d6), δ: 10.08 (s, 1H), 9.20 (s, 1H), 8.99-8.98 (d, J=4.8 Hz, 1H), 8.75-8.74 (d, J=4.8 Hz, 1H), 7.91-7.89 (d, J=5.2 Hz, 1H), 7.39-7.37 (d, J=10.4 Hz, 1H), 6.72-6.71 (d, J=7.2 Hz, 1H), 5.36 (bs, 1H), 2.74-2.73 (d, J=4.0 Hz, 3H). MS (M+1): 348.12.

Workup

  1. customReaction mixture
  2. customReaction mass
  3. customwas quenched with ice water and layers
  4. customwere separated
  5. extractionThe aqueous layer was extracted with EtOAc (3×10 ml)
  6. washThe combined organic extracts were washed with sat NaHCO3 solution and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto get crude product which
  10. customwas purified by column chromatography

Sources & evidence

ORD record
ord-dcea8c24901c4ff1ba7d4c448cb580fe
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

Loading…