Diisopropylethylamine → 3-(2-{1-[4-(6-Methoxy-pyridin-3-yl)-benzoyl]-pyrrolidin-2-(r,s)-yl}-ethyl)-benzonitrile

HRID 901336Notes

Reaction equation

HRID 901336 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH:49]1[CH2:53][CH2:52][CH2:51][CH:50]1[CH2:54][CH2:55][C:56]1[CH:57]=[C:58]([CH:61]=[CH:62][CH:63]=1)[C:59]#[N:60]>CCOC(C)=O.CN(C=O)C>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]([C:13]([N:49]3[CH2:53][CH2:52][CH2:51][CH:50]3[CH2:54][CH2:55][C:56]3[CH:57]=[C:58]([CH:61]=[CH:62][CH:63]=3)[C:59]#[N:60])=[O:15])=[CH:16][CH:17]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 46742594-(6-methoxypyridin-3-yl)benzoic AcidHCID 776287743-(2-Pyrrolidin-2-(r,s)-ylethyl)-benzonitrile

Product 1

HCID 776287523-(2-{1-[4-(6-Methoxy-pyridin-3-yl)-benzoyl]-pyrrolidin-2-(r,s)-yl}-ethyl)-benzonitrileYield 44%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A flask containing 4-(6-Methoxy-pyridin-3-yl)-benzoic acid (0.114 g, 0.5 mmol) and DMF (3 mL) is stirred. To this is added Diisopropylethylamine (87 uL, 0.5 mmol) followed by TBTU (0.16 g, 0.5 mmol) and stirred 2 minutes. A solution of 3-(2-Pyrrolidin-2-(R,S)-ylethyl)-benzonitrile (0.10 g, 0.5 mmol) and DMF (1 mL) is added and the reaction stirred for 24 h. The reaction mixture is diluted with EtOAc (100 mL) and washed with saturated sodium bicarbonate (4×20 mL), brine (25 mL), dried over MgSO4 and concentrated. Purification by flash chromatography (1:1/EtOAc:Hexanes) gives the title compound as a clear oil (0.09 g, 0.22 mmol). 1H NMR (CDCl3, 300 MHz) 8.38(s, 1H), 7.81(d, 1H), 7.65-7.35(m, 8H), 6.83(d, 1H), 4.40-4.25(m, 1H), 3.97(s, 3H), 3.58-3.45(m, 2H), 2.82-2.68(m, 2H), 2.45-2.30(m, 1H), 2.25-2.10(m, 1H), 2.02-1.86(m, 1H), 1.85-1.65(m, 3H).

Workup

  1. stirringstirred 2 minutes
  2. stirringthe reaction stirred for 24 h
  3. washwashed with saturated sodium bicarbonate (4×20 mL), brine (25 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash chromatography (1:1/EtOAc:Hexanes)

Sources & evidence

ORD record
ord-2b5daee4aa1f40e8965dd2bacb1f6c63
Source dataset
uspto-grants-2008_04
Patent number
US07361663B2

Reaction notes

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