Triethylamine → 4-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-3-methyl-piperazin-2-one

HRID 559363Notes

Reaction equation

HRID 559363 reaction equation
Cl.Cl.[OH:3][C@@H:4]1[CH2:11][N:10]([CH2:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][NH:18][CH:17]([CH3:21])[C:16]2=[O:22])[CH2:9][CH2:8][C:5]21[CH2:7][CH2:6]2.[Cl:23][C:24]1[CH:25]=[C:26]([CH:32]=[CH:33][C:34]=1[F:35])[CH:27]=[CH:28][C:29](O)=[O:30].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O>[Cl:23][C:24]1[CH:25]=[C:26](/[CH:27]=[CH:28]/[C:29]([N:18]2[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][CH2:12][N:10]3[CH2:9][CH2:8][C:5]4([CH2:6][CH2:7]4)[C@H:4]([OH:3])[CH2:11]3)[C:16](=[O:22])[CH:17]2[CH3:21])=[O:30])[CH:32]=[CH:33][C:34]=1[F:35]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27736443-(3-Chloro-4-fluorophenyl)prop-2-enoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 669995521-[3-((S)-4-hydroxy-6-aza-spiro[2,5]oct-6-yl)-propyl]-3-methyl-piperazin-2-one dihydrochloride

Product 1

HCID 252041964-[(E)-3-(3-Chloro-4-fluoro-phenyl)-acryloyl]-1-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-3-methyl-piperazin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of crude 1-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-3-methyl-piperazin-2-one dihydrochloride (example 38; 0.03 g, 0.1 mmol) in N,N-dimethylformamide (0.8 ml) was added 3-chloro-4-fluorocinnamic acid (0.02 g, 0.1 mmol), triethylamine (0.05 ml, 0.4 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (0.04 g, 0.1 mmol) and the reaction shaken for 1 h, after which time the reaction mixture was directly purified by preparative HPLC. This afforded the titled product as a colorless gum MS (ISP)=464.3 (M+H)+.

Workup

  1. customafter which time the reaction mixture was directly purified by preparative HPLC

Sources & evidence

ORD record
ord-d7b7de03d576448fb9b675ac1cd2d021
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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