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

HRID 422235Notes

Reaction equation

HRID 422235 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 dying (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. concentrationconcentrating
  5. customPurify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM)

Sources & evidence

ORD record
ord-d6130d8d3d5248939d0cec2502a19159
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

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