4-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-hydroxymethyl-benzonitrile → [5-aminomethyl-2-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']-terpyridin-1'-ylmethyl)-phenyl]-methanol

HRID 1987395Notes

Reaction equation

HRID 1987395 reaction equation
[CH3:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[N:9]2[CH2:21][C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=2[CH2:30][OH:31])=[N:4][CH:5]=[CH:6][CH:7]=1>CO>[NH4+:4].[OH-:31].[NH2:27][CH2:26][C:25]1[CH:28]=[CH:29][C:22]([CH2:21][N:9]2[CH:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[CH2:11][CH2:12][CH2:13][CH:8]2[C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)=[C:23]([CH2:30][OH:31])[CH:24]=1

Participants

4

Reactant 1

HCID 674215664-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-hydroxymethyl-benzonitrile

Product 2

HCID 14923Ammonium HydroxideHCID 67420489[5-aminomethyl-2-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']-terpyridin-1'-ylmethyl)-phenyl]-methanolYield 175.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 4-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-3-hydroxymethyl-benzonitrile (0.610 g, 1.48 mmol) dissolved in MeOH (12 mL) ammonia gas was bubbled for 10 minutes. A pre-washed mixture of Raney Nickel (˜1.5 grams) was added to the nitrile and the mixture was shaken on the hydrogenator at 45 psi for 2.5 hours. The mixture was filtered through a sintered glass funnel containing a celite plug and the filtrated was concentrated in vacuo to a green foam. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 87:8:5, v/v/v) afforded [5-aminomethyl-2-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]-terpyridin-1′-ylmethyl)-phenyl]-methanol as a white foam (0.540 g, 88% ). 1H NMR (CDCl3) δ 1.25 (br s, 1H), 1.62-1.72 (m, 3H), 2.03 (m, 1H), 2.32 (m, 2H), 2H), 2.49 (s, 6H), 2.81 (br s, 1H), 3.55 (s, 2H), 3.62 (s, 1H), 4.01 (d, 2H, J=9.0 Hz), 4.34 (s, 2H), 5.18 (br s, 1H), 6.59 (d, 1H, J=9.0 Hz), 6.72 (d, 1H, J=9.0 Hz), 6.83 (m, 3H), 7.23 (d, 2H, J=9.0 Hz), 8.22 (d, 2H, J=3.0 Hz).

Workup

  1. customwas bubbled for 10 minutes
  2. additionA pre-washed mixture of Raney Nickel (˜1.5 grams)
  3. additionwas added to the nitrile
  4. filtrationThe mixture was filtered through a sintered glass funnel
  5. additioncontaining a celite plug
  6. concentrationthe filtrated was concentrated in vacuo to a green foam
  7. customPurification by column chromatography on silica gel (CH2Cl2

Sources & evidence

ORD record
ord-665dd7e3beee4e51958b26ff7c646272
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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