Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(4-Hydroxymethyl-2,5-dimethylphenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 1468520Notes

Reaction equation

HRID 1468520 reaction equation
[C:1]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]([N:21]([CH3:29])[CH2:22][CH2:23][CH2:24][CH2:25]C(O)=O)=[O:20])[CH2:13][CH2:12]1)=[O:9].[NH2:36][C:37]1[C:42]([CH3:43])=[CH:41][C:40]([CH2:44][OH:45])=[C:39]([CH3:46])[CH:38]=1.C(N(CC)C(C)C)(C)C.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-:69].[Na+]>C(Cl)Cl>[OH:45][CH2:44][C:40]1[C:39]([CH3:46])=[CH:38][C:37]([NH:36][C:25]([CH2:24][CH2:23][CH2:22][N:21]([CH3:29])[C:19]([CH2:18][CH2:17][N:14]2[CH2:13][CH2:12][CH:11]([O:10][C:8](=[O:9])[NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:16][CH2:15]2)=[O:20])=[O:69])=[C:42]([CH3:43])[CH:41]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66770156(4-Amino-2,5-dimethylphenyl)methanolHCID 667703095-({3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}-methylamino)pentanoic acid

Product 1

HCID 66770246Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(4-Hydroxymethyl-2,5-dimethylphenylcarbamoyl)propyl]methylcarbamoyl}ethyl)piperidin-4-yl EsterYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-({3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionyl}-methylamino)pentanoic acid (1.19 g, 2.46 mmol); (4-amino-2,5-dimethylphenyl)-methanol (372 mg, 2.46 mmol) and N,N-diisopropylethylamine (858 μL, 4.93 mmol) in DCM (18.5 mL) was stirred at room temperature for 30 min. N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (708 mg, 3.69 mmol) was added and the resulting mixture was stirred at room temperature for 3 h. Saturated aqueous sodium bicarbonate solution (5 mL) was added and this mixture was extracted with DCM (2×2 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-10% MeOH in DCM) to give the title compound (460 mg, 31% yield) as a yellow oil.

Workup

  1. extractionthis mixture was extracted with DCM (2×2 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-36870655a4d846ab9934ffa015c74caf
Source dataset
uspto-grants-2015_04
Patent number
US09000173B2

Reaction notes

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