Diisopropylethylamine → (S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylate

HRID 409795Notes

Reaction equation

HRID 409795 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]([NH:28][CH3:29])[CH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[Cl:39][C:40]1[C:59]([F:60])=[CH:58][CH:57]=[CH:56][C:41]=1[CH2:42][NH:43][C:44](=[O:55])OC1C=CC([N+]([O-])=O)=CC=1>C1COCC1>[Si:1]([O:8][CH2:9][C@@H:10]([N:28]([CH3:29])[C:44]([NH:43][CH2:42][C:41]1[CH:56]=[CH:57][CH:58]=[C:59]([F:60])[C:40]=1[Cl:39])=[O:55])[CH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 579475384-Nitrophenyl 2-chloro-3-fluorobenzylcarbamateHCID 57947804(S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(methylamino)pentanoyl)piperazine-1-carboxylate

Product 1

HCID 57947925(S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylateYield 62.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(methylamino)pentanoyl)piperazine-1-carboxylate (16 g, 37.3 mmol) and DIEA (1.3 mL, 7.46 mmol) in THF (180 mL) was added 4-nitrophenyl 2-chloro-3-fluorobenzylcarbamate (12 g, 37.3 mmol). The reaction mixture was stirred at RT for 2 h and concentrated. The residue was purified on silica gel using a mixture of EtOAc and hexanes to give (S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylate (14.3 g, 62.4% for three steps). LRMS (M+H) m/z 615.3.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified on silica gel using
  3. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-b78eb50641ee469e99eae76dc6afbd0f
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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