Diisopropylethylamine → 5-cyano-2-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-benzoic acid methyl ester

HRID 1784196Notes

Reaction equation

HRID 1784196 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)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:21][O:22][C:23](=[O:34])[C:24]1[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[CH:26][C:25]=1[CH2:32]Br.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:21][O:22][C:23](=[O:34])[C:24]1[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[CH:26][C:25]=1[CH2:32][N:9]1[CH:8]([C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH2:13][CH2:12][CH2:11][CH:10]1[C:14]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 17965928Methyl 2-(bromomethyl)-5-cyanobenzoateHCID 674211653,3''-Dimethyl-1',2',3',4',5',6'-hexahydro-[2,2'; 6',2'']terpyridine

Product 1

HCID 674204965-cyano-2-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-benzoic acid methyl esterYield 96.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Using General Procedure A: A solution of 3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.260 g, 0.98 mmol), 2-bromomethyl-5-cyano-benzoic acid methyl ester (0.360 g, 1.42 mmol), KI (37 mg, 0.22 mmol), and DIPEA (0.35 mL, 2.01 mmol) in DMF (5 mL) was heated at 60° C. for 17 hours. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH) provided 415 mg (96%) of 5-cyano-2-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester as a tan solid. To a cold (0° C.) solution of 5-cyano-2-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester (0.409 g, 0.937 mmol) in THF (4.5 mL) and MeOH (9 mL) was added LiBH4 (229 mg, 10.52 mmol) and the mixture was allowed to warm to room temperature overnight. The mixture was diluted with 1.0 N NaOH (10 mL) and extracted with CH2Cl2 (5×25 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH) provided 0.332 g (87%) of COMPOUND 29 as a white foam. 1H NMR (CDCl3) δ 1.61-1.77 (m, 3H), 2.05-2.14 (m, 1H), 2.30-2.44 (m, 2H), 2.51 (s, 6H), 3.71 (s, 2H), 4.11 (d, 2H, J=10.8 Hz), 4.46 (s, 2H), 4.94 (br s, 1H), 6.87-6.96 (m, 4H), 7.22-7.27 (m, 3H), 8.21 (d, 2H, J=4.2 Hz). 13C NMR (CDCl3) δ 19.35, 25.70, 28.19, 51.31, 62.24, 67.36, 109.58, 119.48, 122.56, 129.25, 130.02, 132.00, 132.24, 138.53, 139.79, 145.29, 146.76, 159.25; ES-MS m/z 413 (M+H). Anal. Calcd. For C26H28N4O.1.0H2O2: C, 72.53; H, 7.02; N, 13.01. Found: C, 72.46; H, 6.73; N, 12.91.

Workup

  1. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH)

Sources & evidence

ORD record
ord-cd83c06abdbc466b91d443a6d698ad5a
Source dataset
uspto-grants-2009_03
Patent number
US07501518B2

Reaction notes

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