Dichloromethane → N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3'-(methylsulfonyl)biphenyl-4-amine

HRID 1673004Notes

Reaction equation

HRID 1673004 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([NH:6][CH2:7][C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([F:23])([F:22])[F:21])[CH:9]=2)=[CH:4][CH:3]=1.[CH3:26][S:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])=[O:28].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>COCCOC.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:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[N:12]1[C:8]([CH2:7][NH:6][C:5]2[CH:24]=[CH:25][C:2]([C:34]3[CH:33]=[CH:32][CH:31]=[C:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH:35]=3)=[CH:3][CH:4]=2)=[CH:9][C:10]([C:20]([F:23])([F:22])[F:21])=[N:11]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 592401354-bromo-N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)aniline

Product 1

HCID 59240161N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3'-(methylsulfonyl)biphenyl-4-amine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 225 mg of 4-bromo-N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)aniline (0.52 mmol), 160 mg of 3-(methylsulfonyl)phenylboronic acid (0.82 mmol), 27 mg of PdCl2(dppf).CH2Cl2 (33 μmol), and 0.5 mL of 3.5 M aqueous K2CO3 (1.75 mmol) in DME (2.5 mL) was placed in a 5 mL microwave reaction vial and heated to 140° C. for 10 minutes in the Biotage Initiator microwave reactor. After cooling to room temperature the vial was opened and the lower aqueous layer was removed by means of a glass pipet. The resulting dark organic solution was diluted with EtOAc, treated with Na2SO4 filtered and concentrated in vacuo to afford a dark oil. The crude product was purified by silica gel flash chromatography on a 12 g column using gradient elution from 0% to 90% EtOAc/hexane. Appropriate fractions were combined and concentrated in vacuo to afford N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3′-(methylsulfonyl)biphenyl-4-amine as a white foam, yield 150 mg (57%): 1H NMR (400 MHz, CDCl3): δ 8.10-8.06 (m, 1H), 7.83-7.77 (m, 2H), 7.61-7.55 (m, 2H), 7.52-7.41 (m, 5H), 7.67 (s, 1H), 6.64-6.59 (m, 2H); MS (ESI) m/z 506.1 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature the vial
  2. customthe lower aqueous layer was removed by means of a glass pipet
  3. additionThe resulting dark organic solution was diluted with EtOAc
  4. additiontreated with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford a dark oil
  8. customThe crude product was purified by silica gel flash chromatography on a 12 g column
  9. washelution from 0% to 90% EtOAc/hexane
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d665e3511d4048e5a30589fe2fbcd395
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

Loading…