4-(Dimethylamino)Benzaldehyde → 1-(4-(dimethylamino)benzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine

HRID 133601Notes

Reaction equation

[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[C:6]([NH:8][CH2:9][C:10]([NH:12][CH2:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:11])=[O:7].[BH3-]C#N.[Na+].[CH3:29][N:30]([CH3:39])[C:31]1[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=1.C1(N=C=O)C=CC=CC=1>C(#N)C.C(O)(=O)C.CO>[CH3:29][N:30]([CH3:39])[C:31]1[CH:38]=[CH:37][C:34]([CH2:35][N:17]2[CH2:18][CH2:19][CH:14]([CH2:13][NH:12][C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[C:5]3[CH:20]=[CH:21][CH:22]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:4]=3)[CH2:15][CH2:16]2)=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A methanol (1.0 mL) solution of 4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine (20.0 mg, 0.058 mmol) and NaBH3CN (16.5 mg) were added to a 5% acetic acid solution (1.0 mL) of 4-(dimethylamino)benzaldehyde (30.4 mg, 0.204 mmol), and the resulting mixture was stirred at 60° C. for 19 hours. The solvent was evaporated to provide a solid. Acetonitrile (2.0 mL) and phenyl isocyanate (6.9 mg, 0.048 mmol) were added to the solid, and resulting mixture was stirred at 25° C. for 1 hour. The reaction mixture was loaded onto a Varian™ SCX column and washed with methanol (20 mL). The obtained crude product was eluted with a 2 M NH3-methanol (6 mL), and the eluate was concentrated to thereby afford 1-[4-(dimethylamino)benzyl]-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine (Compd. No. 937) as an off-white oil (13.5 mg, 49%). The purity was determined by RPLC/MS (87%). ESI/MS m/e 477.3 (M++H, C25H31F3N4O2).

Workup

customThe solvent was evaporated
customto provide a solid
customresulting mixture
stirringwas stirred at 25° C. for 1 hour
washwashed with methanol (20 mL)
customThe obtained crude product
washwas eluted with a 2 M NH3-methanol (6 mL)
concentrationthe eluate was concentrated to thereby afford 1-[4-(dimethylamino)benzyl]-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine (Compd. No

Sources & evidence

ORD record: ord-266aede8ef0e4d26a2c01d7f1b43f6bd
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07390830B1

Reaction notes

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