Triethylamine → 5-[(4-{(3S)-4-[(1S,2R)-5-Bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidin-1-yl)carbonyl]-4,6-dimethylpyrimidine

HRID 2387461Notes

Reaction equation

HRID 2387461 reaction equation
Cl.Cl.Cl.[Br:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C@@H:10]([N:14]1[CH2:19][CH2:18][N:17]([C:20]3([CH3:26])[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH2:16][C@@H:15]1[CH3:27])[C@H:9]([O:28][CH2:29][CH3:30])[CH2:8]2.[CH3:31][C:32]1[C:37]([C:38](O)=[O:39])=[C:36]([CH3:41])[N:35]=[CH:34][N:33]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.CO.CCOC(C)=O>[Br:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C@H:10]([N:14]1[CH2:19][CH2:18][N:17]([C:20]3([CH3:26])[CH2:21][CH2:22][N:23]([C:38]([C:37]4[C:32]([CH3:31])=[N:33][CH:34]=[N:35][C:36]=4[CH3:41])=[O:39])[CH2:24][CH2:25]3)[CH2:16][C@@H:15]1[CH3:27])[C@H:9]([O:28][CH2:29][CH3:30])[CH2:8]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 149222224,6-Dimethylpyrimidine-5-carboxylic acidHCID 68742760(2S)-1-[(1R,2R)-5-bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-2-methyl-4-(4-methylpiperidin-4-yl)piperazine trihydrochloride

Product 1

HCID 115631965-[(4-{(3S)-4-[(1S,2R)-5-Bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidin-1-yl)carbonyl]-4,6-dimethylpyrimidineYield 80.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a slurry of (2S)-1-[(1R,2R)-5-bromo-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-2-methyl-4-(4-methylpiperidin-4-yl)piperazine trihydrochloride (50 mg, 0.0916 mmol) in methylene chloride (6 mL) were added 4,6-dimethyl-pyrimidine-5-carboxylic acid (27.88 mg, 0.183 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (21.07 mg, 0.11 mmol), 1-hydroxybenzotriazole (13.62 mg, 0.101 mmol) and triethylamine (0.0894 mL, 0.641 mmol). The reaction mixture was stirred at room temperature overnight. Direct chromatography on silica gel with 10% MeOH/EtOAc (1% NH4OH) afforded the desired product (42 mg, 80%). LC-MS [M+1]=570.10; 572.05.

Sources & evidence

ORD record
ord-5c421907174e4cc5a7bad3a97c28ef6c
Source dataset
uspto-grants-2012_09
Patent number
US08268826B2

Reaction notes

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