Triethylamine → 3-Methyl-2-[4-(trifluoromethyl)phenyl]-N-[(R)-2-(2-pyridylmethylamino)-5-indanyl]benzamide

HRID 1531303Notes

Reaction equation

HRID 1531303 reaction equation
[NH2:1][C@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:11][C:12]([C:14]3[C:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=4)=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=3)=[O:13])[CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[N:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH:44]=O.[BH4-]>CO>[N:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH2:44][NH:1][C@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:11][C:12]([C:14]3[C:15]([C:21]4[CH:22]=[CH:23][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:25][CH:26]=4)=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=3)=[O:13])[CH:8]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 142732-PyridinecarboxaldehydeHCID 28123BorohydrideHCID 11112358(r)-n-(2-Aminoindan-5-yl)-6-methyl-4'-trifluoromethylbiphenyl-2-carboxamide

Product 1

HCID 98273433-Methyl-2-[4-(trifluoromethyl)phenyl]-N-[(R)-2-(2-pyridylmethylamino)-5-indanyl]benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The amine is dissolved in methanol (160 mL), triethylamine (1.45 g, 14.4 mmol) and 2-pyridinecarboxaldehyde (1.59 g, 14.8 mmol) are added, and the mixture is stirred overnight. Polymer supported borohydride (Aldrich, borohydride on Amberlite IRA-400, 2.5 mmol/g, 6.0 g, 14.8 mmol) is added and the mixture is stirred for an additional 24 hours. The resin is removed by filtration and the filtrate is concentrated in vacuo. The residue is dissolved in a small amount of ethyl acetate and triturated with hexane to yield (R)-6-methyl4′-trifluoromethylbiphenyl-2-carboxylic acid [2-(2-pyridylmethylamino)-indan-5-yl] amide as a solid. The solid is dissolved in ethanol (100 mL) and a saturated solution of HCl (g) in ethyl ether is added. The resulting solid is collected to yield (R)-6-methyl-4′-trifluoromethylbiphenyl-2-carboxylic acid [2-(2-pyridylmethylamino)-indan-5-yl] amide hydrochloride, m.p. 281-283° C.

Workup

  1. additionis added
  2. stirringthe mixture is stirred for an additional 24 hours
  3. customThe resin is removed by filtration
  4. concentrationthe filtrate is concentrated in vacuo
  5. dissolutionThe residue is dissolved in a small amount of ethyl acetate
  6. customtriturated with hexane

Sources & evidence

ORD record
ord-d9717ef8046a43938737f49314a11677
Source dataset
uspto-grants-2001_03
Patent number
US06197798B1

Reaction notes

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