Triethylamine → HCID 24768912, compound

HRID 2422840Notes

Reaction equation

HRID 2422840 reaction equation
C(N(CC)CC)C.[CH3:8][N:9]1[C:13]([CH3:14])=[C:12]([S:15](Cl)(=[O:17])=[O:16])[C:11]([CH3:19])=[N:10]1.[F:20][C:21]1[CH:22]=[CH:23][C:24]([O:36][CH3:37])=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C@H:33]([NH2:35])[CH3:34])=[CH:29][CH:28]=2)[CH:26]=1>ClCCl>[F:20][C:21]1[CH:22]=[CH:23][C:24]([O:36][CH3:37])=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C@H:33]([NH:35][S:15]([C:12]3[C:11]([CH3:19])=[N:10][N:9]([CH3:8])[C:13]=3[CH3:14])(=[O:17])=[O:16])[CH3:34])=[CH:29][CH:28]=2)[CH:26]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27373401,3,5-trimethyl-1H-pyrazole-4-sulfonyl chlorideHCID 67246165HCID 67246165, compound

Product 1

HCID 24768912HCID 24768912, compoundYield 40.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Palladium acetate (56 mg, 0.25 mmol) was added to a mixture of 5-fluoro-2-methoxyphenylboronic acid (850 mg, 5.0 mmol) and (R)-1-(4-bromophenyl)ethylamine (500 mg, 2.5 mmol) in water (20 ml). This mixture was heated for 5 min at 200° C. in a Smithcreator microwave oven and then diluted with methanol (200 ml). The mixture was purified on a SCX column (20 g) using 2M ammonia in methanol to elute the intermediate amine. Evaporation of solvents under reduced pressure gave (R)-1-(5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine as a gum (580 mg, 2.37 mmol, 96.6%). Triethylamine (41.1 μl, 0.295 mmol) and 1,3,5-trimethyl-1H-pyrazole-4-sulfonyl chloride (20.5 mg, 0.0984 mmol) were added to a solution of (R)-1-(5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine (20 mg, 0.082 mmol) in dichloromethane (1 ml) and the resulting solution shaken at room temperature overnight. The reaction mixture was washed with saturated sodium bicarbonate solution (500 μl), the dichloromethane layer separated, dried over magnesium sulfate and the solvent evaporated. Purification by preparatory LCMS and removal of solvent under reduced pressure gave the title compound (13.8 mg, 0.033 mmol, 40%): 1H NMR (400 MHz, CDCl3): δ7.37, 7.14 (a/b, 4H), 7.02-6.87 (m, 3H), 4.68 (m, 1H), 4.48 (t, 1H), 3.78 (s, 3H), 3.55 (s, 3H), 2.35 (s, 3H), 2.22 (s, 3H), 1.50 (d, 3H) ppm; MS (ESI) m/z: 417 [M+H]+.

Workup

  1. washThe reaction mixture was washed with saturated sodium bicarbonate solution (500 μl)
  2. customthe dichloromethane layer separated
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent evaporated
  5. customPurification
  6. customby preparatory LCMS and removal of solvent under reduced pressure

Sources & evidence

ORD record
ord-7838091d1c684d6eb929fdacf6dd166e
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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