Ammonia → 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4tetrahydroisoquinolin-6-yl)-amide

HRID 1954424Notes

Reaction equation

HRID 1954424 reaction equation
CS(Cl)(=O)=O.O[CH2:7][CH2:8][C:9]1[CH:10]=[C:11]([NH:17][C:18]([C:20]2[C:21]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:19])[CH:12]=[CH:13][C:14]=1[CH2:15]O.C([N:38](CC)CC)C.N>C1COCC1>[CH2:15]1[C:14]2[C:9](=[CH:10][C:11]([NH:17][C:18]([C:20]3[C:21]([C:26]4[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=4)=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:19])=[CH:12][CH:13]=2)[CH2:8][CH2:7][NH:38]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 15491254HCID 15491254, compound

Product 1

HCID 110147584'-Trifluoromethyl-biphenyl-2-carboxylic acid (1,2,3,4tetrahydroisoquinolin-6-yl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Methanesulfonyl chloride (0.085 mL) was added to a 0° C. solution of 4'-trifluoromethyl-biphenyl-2-carboxylic acid-[3-(2-hydroxy-ethyl)-4-hydroxymethyl-phenyl]-amide (214 mg, 0.51 mmol) and triethylamine (0.18 mL) in THF (8.5 mL). TLC showed complete reaction after 30 min. The contents were cooled to -78° C., excess ammonia was added, and the contents were stirred for 18 hrs at 25° C. The solvents were removed under vacuum, methylene chloride (10 mL) and aqueous 1N HCl were added and the contents were stirred for 1 hr. The phases were separated and the aqueous phase was rendered alkaline with aqueous sodium hydroxide to a pH of 12. The organic phase was extracted with methylene chloride (4×10 mL), the solvent removed under vacuum to give a white solid (108 mg) which was chromatographed on silica eluting with 5% methanol/methylene chloride with 0.5% ammonium hydroxide. The product was obtained as a white solid (40 mg, 20%).

Workup

  1. customreaction after 30 min
  2. customThe solvents were removed under vacuum, methylene chloride (10 mL) and aqueous 1N HCl
  3. additionwere added
  4. stirringthe contents were stirred for 1 hr
  5. customThe phases were separated
  6. extractionThe organic phase was extracted with methylene chloride (4×10 mL)
  7. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-f87f4c9f1feb4258808d659100794aba
Source dataset
uspto-grants-2000_09
Patent number
US06121283

Reaction notes

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