4-Methylmorpholine → 2-{1-(4-Fluorobenzyl)-2-[2-methoxymethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2-oxo-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 720205Notes

Reaction equation

HRID 720205 reaction equation
Cl.[NH2:2][CH:3]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[C:13]([NH:15][CH3:16])=[O:14])[CH2:8][CH:7]1[CH2:28][O:29][CH3:30])=[O:5].[C:39]([N:46]1[CH2:53][CH2:52][CH2:51][C@H:47]1[C:48](O)=[O:49])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40].ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C.O.CCOC(C)=O>[C:42]([O:41][C:39]([N:46]1[CH2:53][CH2:52][CH2:51][CH:47]1[C:48](=[O:49])[NH:2][CH:3]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH:12]([C:13](=[O:14])[NH:15][CH3:16])[CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:8][CH:7]1[CH2:28][O:29][CH3:30])=[O:5])=[O:40])([CH3:45])([CH3:44])[CH3:43]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 695877352-{4-[2-amino-3-(4-fluorophenyl)-propionyl]-3-methoxymethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propionamide HCl

Product 1

HCID 695878592-{1-(4-Fluorobenzyl)-2-[2-methoxymethyl-4-(1-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-piperazin-1-yl]-2-oxo-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-{4-[2-Amino-3-(4-fluorophenyl)-propionyl]-3-methoxymethyl-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propionamide HCl, 66, (0.36 g, 0.55 mmol) and BOC-L-Proline (0.13 g, 0.6 mmol) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.2 g, 1.1 mmol) and 1-hydroxybenzotriazole (0.1 g, 0.7 mmol) are dissolved in anhydrous DMF (1.5 mL). The reaction mixture is cooled to 0° C., then N-methylmorpholine (0.5 mL, 4.1 mmol) is added. The reaction mixture is placed in a refrigerator overnight. EtOAc (25 mL) and water (75 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×30 mL). All organic layers are combined and washed with water (2×50 mL), and dried over Na2SO4. The solvent is removed in vacuo to afford 0.39 g of the desired product.

Workup

  1. customis placed in a refrigerator overnight
  2. customthe organic layer is separated
  3. extractionThe aqueous layer is extracted with EtOAc (3×30 mL)
  4. washwashed with water (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-fd438457a0684b7d8f52564e6f2fdeaf
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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