1,2-Dichloroethane → HCID 25103397, compound

HRID 884665Notes

Reaction equation

HRID 884665 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=[O:14])[CH:11]=[C:10]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([CH3:22])[CH:16]=3)[CH:9]=2)=[C:4]([CH3:23])[CH:3]=1.ClCCCl.C([N:35]1[CH2:40][CH2:39][CH:38]([CH:41]=O)[CH2:37][CH2:36]1)(OC(C)(C)C)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[OH:21][C:18]1[CH:19]=[CH:20][C:15]([C:10]2[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][CH2:41][CH:38]4[CH2:39][CH2:40][NH:35][CH2:36][CH2:37]4)=[CH:3][C:4]=3[CH3:23])[NH:13][C:12](=[O:14])[CH:11]=2)=[CH:16][C:17]=1[CH3:22]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 59348958HCID 59348958, compound

Product 1

HCID 25103397HCID 25103397, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In a round bottom flask was added 6-(4-amino-2-methylphenyl)-4-(4-hydroxy-3-methylphenyl)pyridin-2(1H)-one (76 mg, 0.25 mmol), 1,2 Dichloroethane (5.0 mL), acetic acid (0.1 mL), and N-Boc-4-Formyl piperidine (0.65 mg, 0.30 mmol). The reaction was stirred at room temperature for 15 minutes before adding sodium triacetoxy borohydride (85 mg, 0.40 mmol). Stirring was continued at room temperature for 10 min. The reaction was then concentrated down under reduced pressure. The resulting oil was then dissolved in 4N HCl/dioxane (5.0 mL) and stirred at 45° C. for 1 h. The resulting slurry was cooled down to room temperature and the precipitate was filtered off. The resulting solid was then dissolved in MeOH and purified by preparatory HPLC (15-40% gradient of NH4OAc/ACN) to give 4-(4-hydroxy-3-methylphenyl)-6-{2-methyl-4-[(piperidin-4-ylmethyl)amino]phenyl}pyridin-2(1H)-one as the acetate salt (16 mg, 14% yield over 2 steps). 1H NMR (400 MHz, d6-DMSO) δ 7.47 (s, 1H), 7.39 (dd, 1H), 7.06 (d, 1H), 6.85 (d, 1H), 6.45 (m, 2H), 6.36 (s, 1H), 6.27 (s, 1H), 5.95 (t, 1H), 2.98 (m, 2H), 2.91 (t, 1H), 2.48 (m, 2H), 2.22 (s, 3H), 2.16 (s, 3H), 1.72 (m, 4H), 1.09 (m, 1H); MS (EI) for C25H29N3O2: 404 (MH+).

Workup

  1. stirringStirring
  2. waitwas continued at room temperature for 10 min
  3. concentrationThe reaction was then concentrated down under reduced pressure
  4. dissolutionThe resulting oil was then dissolved in 4N HCl/dioxane (5.0 mL)
  5. stirringstirred at 45° C. for 1 h
  6. temperatureThe resulting slurry was cooled down to room temperature
  7. filtrationthe precipitate was filtered off
  8. dissolutionThe resulting solid was then dissolved in MeOH
  9. custompurified by preparatory HPLC (15-40% gradient of NH4OAc/ACN)

Sources & evidence

ORD record
ord-fe6fd903e1d1402e86e6447c59a0181d
Source dataset
uspto-grants-2012_08
Patent number
US08242129B2

Reaction notes

Loading…