Triethylamine → HCID 23658390, compound

HRID 541092Notes

Reaction equation

HRID 541092 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:12]2[CH2:16][C:15]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=3)([C:17]([F:20])([F:19])[F:18])[O:14][N:13]=2)=[C:6]2[C:11]=1C=NC=C2.[NH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1.C([N:39]([CH2:42][CH3:43])[CH2:40][CH3:41])C.[C]=[O:45]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:28][C:23]1[CH:22]=[C:21]([C:15]2([C:17]([F:20])([F:19])[F:18])[O:14][N:13]=[C:12]([C:5]3[CH:6]=[CH:11][C:2]([C:3]([NH:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=4)=[O:45])=[C:41]4[C:4]=3[CH:43]=[CH:42][N:39]=[CH:40]4)[CH2:16]2)[CH:26]=[C:25]([Cl:27])[CH:24]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 195092-PyridinemethanamineHCID 86645282HCID 86645282, compound2×HCID 178418416HCID 178418416, compound

Product 1

HCID 23658390HCID 23658390, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 8-bromo-5-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]isoquinoline (i.e. the product from Step C) (20 mg, 0.04 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf)) (6 mg, 0.008 mmol), 2-(aminomethyl)pyridine (17 mg, 0.16 mmol) and triethylamine (0.1 mL, 0.7 mmol) in toluene (2 mL) was purged with carbon monoxide for 15 minutes. Then the reaction vial was maintained with carbon monoxide using a balloon. The reaction mixture was stirred at 70° C. under carbon monoxide atmosphere overnight. The mixture was cooled to room temperature, filtered through a short pad of Celite® diatomaceous filter and rinsed with small amount of ethyl acetate. The filtrate was concentrated and the residue was purified by column chromatography on silica gel using hexanes/ethyl acetate as eluent to provide the title product, a compound of the present invention, as a pale white solid (15 mg).

Workup

  1. customwas purged with carbon monoxide for 15 minutes
  2. customThen the reaction
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through a short pad of Celite®
  5. filtrationdiatomaceous filter
  6. washrinsed with small amount of ethyl acetate
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-9c8cc3fab65145d4ac7a516166ca2c07
Source dataset
uspto-grants-2014_10
Patent number
US08871941B2

Reaction notes

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