Triethylamine → (r)-5-Chloro-1,3-dimethyl-1h-pyrazole-4-sulfonic acid [1-(5'-chloro-2'-ethoxy-biphenyl-4-yl)-ethyl]-amide

HRID 2422837Notes

Reaction equation

HRID 2422837 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][CH3:19])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]([NH2:16])[CH3:15])=[CH:10][CH:9]=2)[CH:7]=1.C(N(CC)CC)C.[Cl:27][C:28]1[N:32]([CH3:33])[N:31]=[C:30]([CH3:34])[C:29]=1[S:35](Cl)(=[O:37])=[O:36]>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:18][CH3:19])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C@H:14]([NH:16][S:35]([C:29]3[C:30]([CH3:34])=[N:31][N:32]([CH3:33])[C:28]=3[Cl:27])(=[O:36])=[O:37])[CH3:15])=[CH:10][CH:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27771265-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chlorideHCID 672454021-(5'-Chloro-2'-ethoxy-biphenyl-4-yl)-ethylamine

Product 1

HCID 16202171(r)-5-Chloro-1,3-dimethyl-1h-pyrazole-4-sulfonic acid [1-(5'-chloro-2'-ethoxy-biphenyl-4-yl)-ethyl]-amideYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 5-chloro-2-ethoxyphenylboronic acid (601 mg, 3.0 mmol), palladium (II) acetate (33 mg, 0.15 mmol) and (R)-1-(4-bromophenyl)ethylamine (295 mg, 1.5 mmol) in water (4 ml) was heated for 5 min at 200° C. in a Smithcreator microwave oven. The reaction mixture was diluted with dichloromethane and purified on a Strata™ 5 g/20 ml SCX column (eluted with 2M ammonia in methanol) to give (R)-1-(5′-chloro-2′-ethoxy-biphenyl-4-yl)-ethylamine (341 mg, 1.2 mmol, 82%). To a solution of 1-(5′-chloro-2′-ethoxy-biphenyl-4-yl)-ethylamine (30 mg, 0.1 mmol) in dichloromethane (0.75 ml) was added triethylamine (36 mg, 0.35 mmol) and 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonyl chloride (30 mg, 0.13 mmol) in dichloromethane (0.5 ml). The reaction mixture was then agitated at room temperature for 16 h and quenched with acetic acid (200 μl). Purification by preparatory LCMS and removal of solvent under reduced pressure gave the title compound (21 mg, 0.04 mmol, 40%): 1H NMR (400 MHz, DMSO-d6): δ 8.25 (d, 1H), 7.32-7.37 (m, 3H), 7.21-7.24 (m, 3H), 7.10 (d, 1H), 4.35 (m, 1H), 4.05 (m, 2H), 2.20 (s, 3H), 1.26-1.35 (m, 6H) ppm; MS (ESI) m/z: value [M+H]+.

Workup

  1. customquenched with acetic acid (200 μl)
  2. customPurification
  3. customby preparatory LCMS and removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-87fa5a37aaf0429f88001ca4a8214743
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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