Formaldehyde → 6-{1-[(2,2-Diphenyl-ethyl)-methyl-amino]-indan-5-yloxy}-nicotinamide

HRID 747988Notes

Reaction equation

HRID 747988 reaction equation
C=O.[BH3-][C:4]#N.[Na+].[C:7]1([CH:13]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:14][NH:15][CH:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:34]=[CH:33][C:29]([C:30]([NH2:32])=[O:31])=[CH:28][N:27]=4)=[CH:22][CH:23]=3)[CH2:18][CH2:17]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>CC(O)=O.CO>[C:35]1([CH:13]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:14][N:15]([CH3:4])[CH:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:34]=[CH:33][C:29]([C:30]([NH2:32])=[O:31])=[CH:28][N:27]=4)=[CH:22][CH:23]=3)[CH2:18][CH2:17]2)[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 113629086-[1-(2,2-Diphenyl-ethylamino)-indan-5-yloxy]-nicotinamide

Product 1

HCID 112482536-{1-[(2,2-Diphenyl-ethyl)-methyl-amino]-indan-5-yloxy}-nicotinamideYield 65.2%

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

Add paraformaldehyde (57 mg) and NaBH3CN (46 mg, 0.734 mmol) to a solution of 6-[1-(2,2-Diphenyl-ethylamino)-indan-5-yloxy)-nicotinamide (example 9, 110 mg, 0.245 mmol) in 5% AcOH/MeOH (3 ml) and stir at ambient temperature for two days. Concentrate the reaction mixture and partition remaining residue between EtOAc and 1M aq. K2CO3. Separate layers and wash organic with 1M aq. K2CO3 and brine before drying (MgSO4) and concentrating. Purify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM) to obtain 74 mg of the title compound as a white solid. Mass spectrum (ion spray): m/z=464 (M+1); 1HNMR (CDCl3): 8.54 (s, 1H), 8.15 (d, 1H), 7.30-7.15 (m, 10H), 6.95-6.81 (m, 4H), 5.81 (br. s, 2H), 4.39 (t, 1H), 4.20 (t, 1H), 3.02 (d, 2H), 2.94-2.75 (m, 2H), 2.27 (s, 3H), 2.06 (m, 2H).

Workup

  1. concentrationConcentrate the reaction mixture
  2. custompartition
  3. washSeparate layers and wash organic with 1M aq. K2CO3 and brine
  4. dry with materialbefore drying (MgSO4)
  5. concentrationconcentrating
  6. customPurify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM)

Sources & evidence

ORD record
ord-dab268fd21c548e7b8c1a52c9d727604
Source dataset
uspto-grants-2008_07
Patent number
US07399774B2

Reaction notes

Loading…