Dichloromethane → Quinoline-6-carboxylic acid (1-benzyl-2-hydroxy-3-{3-[-phenyl-1-(3-phenyl-propyl)-butylcarbamoyl]-piperidin-1-yl}-propyl)-amide

HRID 843323Notes

Reaction equation

HRID 843323 reaction equation
C1([CH2:7][CH2:8][CH2:9][CH:10]([NH:20][C:21]([CH:23]2[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][CH:30]([OH:40])[CH:31]([NH2:39])[CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:24]2)=[O:22])[CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)C=CC=CC=1.[N:41]1[C:50]2[C:45](=[CH:46][C:47]([C:51]([OH:53])=O)=[CH:48][CH:49]=2)[CH:44]=[CH:43][CH:42]=1.C(N([CH2:59][CH3:60])CC)C.Cl.CN(C)[CH2:64][CH2:65][CH2:66]N=C=NCC.[CH2:73](Cl)Cl>>[CH2:32]([CH:31]([NH:39][C:51]([C:47]1[CH:46]=[C:45]2[C:50](=[CH:49][CH:48]=1)[N:41]=[CH:42][CH:43]=[CH:44]2)=[O:53])[CH:30]([OH:40])[CH2:29][N:25]1[CH2:26][CH2:27][CH2:28][CH:23]([C:21](=[O:22])[N:20]([C:60]2[CH:59]=[CH:64][CH:65]=[CH:66][CH:73]=2)[CH:10]([CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:9][CH2:8][CH3:7])[CH2:24]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 825716-Quinolinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 187274631-(3-Amino-2-hydroxy-4-phenyl-butyl)-piperidine-3-carboxylic acid [4-phenyl-1-(3-phenyl-propyl)-butyl]-amide

Product 1

HCID 90923382Quinoline-6-carboxylic acid (1-benzyl-2-hydroxy-3-{3-[-phenyl-1-(3-phenyl-propyl)-butylcarbamoyl]-piperidin-1-yl}-propyl)-amide

Procedure

1-(3-Amino-2-hydroxy-4-phenyl-butyl)-piperidine-3-carboxylic acid [4-phenyl-1-(3-phenyl-propyl)-butyl]-amide (20) (150 mg; 0.28 mmol) is dissolved in methylene chloride (10 mL) at ambient temperature. 6-Quinolinecarboxylic acid (48 mg; 0.28 mmol), triethylamine (0.0772 mL; 0.55 mmol), and N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (58.4 mg; 0.31 mmol) are added sequentially. The mixture is stirred for 18 hours at ambient temperature then concentrated in vacuo at 30° C. The residue is diluted with ethyl acetate (100 mL) and washed successively with water (50 mL), saturated aqueous sodium bicarbonate (50 mL), and saturated brine (50 mL). The organic layer is dried over MgSO4, filtered, and concentrated in vacuo. The residue is purified via silica gel chromatography with gradient elution (2%→20% methanol in methylene chloride) affording the desired product diastereomers (70 mg) as an oil. ESMS: MH+ 697.6 (base).

Workup

  1. concentrationthen concentrated in vacuo at 30° C
  2. additionThe residue is diluted with ethyl acetate (100 mL)
  3. washwashed successively with water (50 mL), saturated aqueous sodium bicarbonate (50 mL), and saturated brine (50 mL)
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified via silica gel chromatography with gradient elution (2%→20% methanol in methylene chloride)

Sources & evidence

ORD record
ord-4d0bef1471ae4abb837840cb6e83cf86
Source dataset
uspto-grants-2002_04
Patent number
US06376514B1

Reaction notes

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