(3S)-(+)-1-Benzyl-3-aminopyrrolidine → (3S)-6-(4-[(1-Benzyl-pyrrolidin-3-ylamino)-methyl]-phenoxy}-nicotinamide

HRID 228221Notes

Reaction equation

HRID 228221 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=2)=[CH:5][CH:4]=1)=O.[CH2:19]([N:26]1[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[BH4-].[Na+]>CO>[CH2:19]([N:26]1[CH2:30][CH2:29][C@H:28]([NH:31][CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[CH:5][CH:4]=2)[CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 1519353(3S)-(+)-1-Benzyl-3-aminopyrrolidineHCID 4311764Sodium borohydrideHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide2×

Product 1

HCID 59729967(3S)-6-(4-[(1-Benzyl-pyrrolidin-3-ylamino)-methyl]-phenoxy}-nicotinamideYield 43.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Using a method similar to Example 334, and using 6-(4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.300 g, 1.24 mmol), (3S)-1-benzylpyrrolidin-3yl amine (0.21 mL, 1.22 mmol), and sodium borohydride (0.108 g, 2.85 mmol) in methanol (12 mL) provides 0.214 g (43%) of the title compound as a white foam (chromatography solvent: ethyl acetate→19:1 ethyl acetate:methanol): high resolution mass spectrum (electrospray): m/z calc for C24H27N4O2 403.2134, found 403.2144; 1H NMR (methanol-d4): 8.66 (d, 1H, J=2.4 Hz), 8.29 (dd, 1H, J=2.9, 8.8 Hz), 7.48-7.42 (m, 2H), 7.40-7.27 (m, 5H), 7.17-7.12 (m, 2H), 7.02 (d, 1H, J=9.3 Hz), 3.79 (d, 1H, J=13.2 Hz), 3.76 (d, 1H, J=13.7 Hz), 3.69 (d, 1H, J=12.7 Hz), 3.67 (d, 1H, J=12.7 Hz), 3.44-3.36 (m, 1H), 2.92 (dd, 1H, J=7.3, 9.8 Hz), 2.69 (t, 2H, J=6.8 Hz), 2.44 (dd, 1H, J=6.3, 10.2 Hz), 2.25-2.14 (m, 1H), 1.77-1.67 (m, 1H).

Sources & evidence

ORD record
ord-72d3f6512d4949778dd60f5079da8c52
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

Loading…