4-bromo-N,N-diethylbenzamide → HCID 9871975, compound

HRID 2304533Notes

Reaction equation

HRID 2304533 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH3:18])[CH2:12][CH2:11]2)[CH:6]=[CH:7][CH:8]=1.[CH2:19]([N:21]([CH2:31][CH3:32])[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=1)[CH3:20].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:31]([N:21]([CH2:19][CH3:20])[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH3:18])[CH2:12][CH2:11]2)=[CH:25][CH:24]=1)[CH3:32]

Participants

7

Reactant 3

HCID 44982544-bromo-N,N-diethylbenzamideHCID 12017125HCID 12017125, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 9871975HCID 9871975, compoundYield 53.6%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 3.5 g (14.1 mmol) of N-(3-methoxyphenyl)-1-propyl-4-piperidinamine, 3.61 g (14.1 mmol) of N,N-diethyl-4-bromobenzamide, 129 mg (0.141 mmol) tris(dibenzylideneacetone)-dipalladium(0) (Pd2dba3), 263 mg (0.423 mmol) of (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (+BINAP) and 1.89 g (19.7 mmol) of sodium t-butoxide in 25 mL of dry toluene was heated at 110° C. under Ar in a pressure vessel for 16 h. The mixture was cooled and partitioned between CH2Cl2 and H2O. The organic layer was washed with brine, dried (K2CO3) and the solvent was evaporated. The residue was chromatographed on a Biotage Flash 75 unit using CH2Cl2:MeOH:NH4OH, 92:8:0.8 as eluent. There was obtained 3.2 g (53% yield) of N,N-diethyl-4-[3-methoxyphenyl(1-propylpiperidin-4yl)amino]benzamide as a solid. A fumarate salt was prepared out of 2-PrOH: mp 168-169° C. MS m/z=424 (M++H). 300 MHz 1H NMR (DMSO-d6) δ7.3 (t, 1H); 7.2 (d, 2H); 6.8 (d, 1H); 6.6 (m, 4H); 6.5 (s, 2H); 4.0 (m, 1H); 3.75 (s, 3H); 3.3 (q, 4H); 3.1 (d, 2H); 2.4 (m, 4H); 1.9 (d, 2H); 1.4 (m, 4H); 1.1 (t, 6H); 0.8 (t, 3H). Anal calcd. for C26H37N3O2.C4H4O4: C, 66.77; H, 7.65; N, 7.78. Found: C, 66.69; H, 7.76; N 7.68.

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between CH2Cl2 and H2O
  3. washThe organic layer was washed with brine
  4. dry with materialdried (K2CO3)
  5. customthe solvent was evaporated
  6. customThe residue was chromatographed on a Biotage Flash 75 unit

Sources & evidence

ORD record
ord-f34206e359de4504afcfaf2b0a3f22ea
Source dataset
uspto-grants-2002_08
Patent number
US06436959B1

Reaction notes

Loading…