Triethylamine → 4-(3-{2-[Tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-acetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1267912Notes

Reaction equation

HRID 1267912 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:17][C:18]([OH:20])=O)[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([CH3:56])=[C:52]([NH2:57])[CH:51]=2)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37]>O1CCCC1>[C:36]([O:40][C:41]([N:43]1[CH2:44][CH2:45][N:46]([CH2:49][C:50]2[CH:55]=[CH:54][C:53]([CH3:56])=[C:52]([NH:57][C:18](=[O:20])[CH2:17][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]3[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=3)[CH:51]=2)[CH2:47][CH2:48]1)=[O:42])([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62365Isobutyl chloroformateHCID 18542398[tert-Butoxycarbonyl-(3,4-difluorophenyl)-amino]-acetic acidHCID 53635909HCID 53635909, compound

Product 1

HCID 120432244-(3-{2-[Tert-butoxycarbonyl-(3,4-difluoro-phenyl)-amino]-acetylamino}-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of [tert-butoxycarbonyl-(3,4-difluorophenyl)-amino]-acetic acid (0.200 g) in tetrahydrofuran (2 ml) at 0° C. was added triethylamine (110 ul) followed by dropwise addition of isobutylchloroformate (100 ul). After stirring for 1 hr, triethylamine (150 ul) was added followed by 4-(3-amino-4-methyl-benzyl)-piperazine-1-carboxylic acid tert-butyl ester (0.234 g) in tetrahydrofuran (2 ml), and the reaction warmed to room temperature and then heated at 58° C. overnight. After cooling to room temperature, the reaction mixture was filtered through Celite, the filtrate collected and the solvent removed in vacuo. Purification by NPHPLC (0-5% MeOH in CH2Cl2) afforded the sub-title compound as a pale yellow solid (0.300 g).

Workup

  1. temperatureheated at 58° C. overnight
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction mixture was filtered through Celite
  4. customthe filtrate collected
  5. customthe solvent removed in vacuo
  6. customPurification by NPHPLC (0-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-4b0e42370cd24a5c825cad04cb47a7f1
Source dataset
uspto-grants-2003_04
Patent number
US06555541B1

Reaction notes

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