Diisopropylethylamine → 4-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-2-fluoro-benzonitrile

HRID 1987341Notes

Reaction equation

HRID 1987341 reaction equation
[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H: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.Br[CH2:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([F:31])[CH:24]=1.CCN(C(C)C)C(C)C>CC#N>[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[N:9]2[CH2:22][C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([F:31])[CH:24]=2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27784664-Cyano-3-fluorobenzyl bromideHCID 575911373,3''-Dimethyl-1',2',3',4',5', 6'-hexahydro-cis-[2,2';6',2'']terpyridine

Product 1

HCID 674219844-((2'R,6'S)-3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-2-fluoro-benzonitrileYield 100%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (2′R,6′S)-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.267 g, 1.00 mmol), 4-bromomethyl-2-fluoro-benzonitrile (0.321 g, 0.1.50 mmol), DIPEA (0.259 g, 2.00 mmol) and KI (0.017 g, 0.10 mmol) in dry CH3CN (10 mL) was stirred at 60° C. for 16 h. After that period of time the CH3CN was removed by evaporation under vacuum, and saturated aqueous NaHCO3 (20 mL) was added. The aqueous mixture was extracted with CH2Cl2 (3×30 mL, and the extract was dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified on a silica gel column (1000:30:1, CH2Cl2/CH3OH/NH4OH), affording 4-((2′R,6′S)-3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-2-fluoro-benzonitrile as a white foam (0.400 g, 100%). 1H NMR (CDCl3) δ 1.65-1.80 (m, 3H), 2.09-2.14 (m, 1H), 2.20-2.38 (m, 2H), 2.44 (s, 6), 3.58 (s, 2H), 4.16 (s, 1H), 4.20 (s, 1H), 6.37-6.43 (m, 2H), 6.93-7.03 (m, 3H), 7.23 (d, 2H, J=7.5 Hz), 8.35 (dd, 2H, J=0.9, 4.5 Hz).

Workup

  1. customAfter that period of time the CH3CN was removed by evaporation under vacuum, and saturated aqueous NaHCO3 (20 mL)
  2. additionwas added
  3. extractionThe aqueous mixture was extracted with CH2Cl2 (3×30 mL
  4. dry with materialthe extract was dried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed by evaporation under vacuum
  7. customthe residue was purified on a silica gel column (1000:30:1, CH2Cl2/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-99da000722ad406e9635bd1b0cac16e2
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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