Potassium Carbonate → (2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide

HRID 1785991Notes

Reaction equation

HRID 1785991 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C@H:29]([N:36]([C:44](=[O:46])[CH3:45])[C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=4)[CH2:28][C@@H:27]3[CH3:47])=[O:25])=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.ClC1C=CC(N([C@H]2C3C(=CC=CC=3)N(C(=O)C3C=CC(O)=CC=3)[C@@H](C)C2)C(=O)C)=CC=1.C([O-])([O-])=O.[K+].[K+].C(OC(N1CCN(CCCCl)CC1)=O)(C)(C)C>CN(C=O)C>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]([N:36]([C@H:29]2[C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:26]([C:24](=[O:25])[C:21]3[CH:22]=[CH:23][C:18]([O:17][CH2:16][CH2:15][CH2:14][N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[CH:19][CH:20]=3)[C@@H:27]([CH3:47])[CH2:28]2)[C:44](=[O:46])[CH3:45])=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 53412057tert-Butyl 4-(3-chloropropyl)piperazine-1-carboxylateHCID 58859774N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]acetamideHCID 68920771(2S,4R)-4-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57595444(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamideYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(2S,4R)-N-(4-Chloro-phenyl)-N-{2-methyl-1-[4-(3-piperazin-1-yl-propoxy)-benzoyl]-1,2,3,4-tetrahydro-quinolin-4-yl}-acetamide was prepared from (2S,4R)-4-[3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester. (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.40 g, 0.92 mmol) was dissolved in DMF at room temperature and K2CO3 (0.127 g, 0.921 mmol) was added. 4-(3-Chloro-propyl)-piperazine-1-carboxylic acid tert-butyl ester (0.242 g, 0.921 mmol) was added and the reaction was allowed to heat to 80° C. overnight. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water, then extracted three times with ethyl acetate, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography to afford the product as colorless oil in 50% yield. (2S,4R)-4-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester (246 mg) was dissolved in 4M HCl in dioxane (2 mL). The mixture was stirred for 2 h at room temperature. After concentration, the white solid was washed with EtOAc to provide the title compound in 100% yield.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and water
  3. extractionextracted three times with ethyl acetate
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated down
  7. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f453b0676496406c9cd3738e011c6da1
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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