Triethylamine → (E)-N-{(S)-2-[4-(4-chloro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl}-3-(5-cyano-2-methoxy-phenyl)-acrylamide

HRID 434302Notes

Reaction equation

HRID 434302 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:14][CH3:15])=[C:7](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)[CH:8]=1)#[N:2].C(N(CC)CC)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[NH2:46][C@H:47]([CH2:64][OH:65])[CH2:48][N:49]1[CH2:54][CH2:53][CH:52]([C:55]([C:57]2[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=2)=[O:56])[CH2:51][CH2:50]1>ClCCl>[Cl:63][C:60]1[CH:61]=[CH:62][C:57]([C:55]([CH:52]2[CH2:53][CH2:54][N:49]([CH2:48][C@H:47]([NH:46][C:11](=[O:13])/[CH:10]=[CH:9]/[C:7]3[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=3[O:14][CH3:15])[CH2:64][OH:65])[CH2:50][CH2:51]2)=[O:56])=[CH:58][CH:59]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11458357(E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acidHCID 68809448[1-((S)-2-amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-chloro-phenyl)-methanone hydrochloride

Product 1

HCID 68809530(E)-N-{(S)-2-[4-(4-chloro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl}-3-(5-cyano-2-methoxy-phenyl)-acrylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (0.31 g, 1.55 mmol), triethylamine (0.2 ml, 1.55 mmol) and 2-(1H benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate (0.49 g 1.55 mmol) in dichloromethane (5 ml), is added to a solution of [1-((S)-2-amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-chloro-phenyl)-methanone hydrochloride and triethylamine (0.4 ml, 3.1 mmol) in dichloromethane (5 ml), and the reaction mixture stirred at ambient temperature for 1 hour. The reaction mixture is diluted with dichloromethane (20 ml), washed successively with saturated sodium bicarbonate solution (25 ml) and brine (25 ml), then dried over magnesium sulphate. The solvent is evaporated and the crude residue purified by flash silica chromatography (methanol:dichloromethane; 5:95) to afford (E)-N-{(S)-2-[4-(4-chloro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl}-3-(5-cyano-2-methoxy-phenyl)-acrylamide. [MH]+482.2.

Workup

  1. washwashed successively with saturated sodium bicarbonate solution (25 ml) and brine (25 ml)
  2. dry with materialdried over magnesium sulphate
  3. customThe solvent is evaporated
  4. customthe crude residue purified by flash silica chromatography (methanol:dichloromethane; 5:95)

Sources & evidence

ORD record
ord-3d9ba8ac63af487a80b82a2c3014f907
Source dataset
uspto-grants-2003_12
Patent number
US06670379B2

Reaction notes

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