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

HRID 341017Notes

Reaction equation

HRID 341017 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]([N:16]([CH3:29])[C:17]([NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=1[Cl:28])=[O:18])[CH2:11][CH2:12][C:13](O)=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:54]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55].CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O.CCOCC>[Si:1]([O:8][CH2:9][C@@H:10]([N:16]([CH3:29])[C:17]([NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=1[Cl:28])=[O:18])[CH2:11][CH2:12][C:13]([N:64]1[CH2:63][CH2:62][N:61]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:66][CH2:65]1)=[O:14])([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57947957(S)-5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoic acid

Product 1

HCID 57947925(S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylateYield 68.3%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (S)-5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoic acid (4.46 g, 10 mmol, 1.0 equiv.) in DMF (50 mL), was added HBTU (5.69 g, 15 mmol, 1.5 equiv.), 1-N-Boc-piperazine (2.79 g, 15 mmol, 1.5 equiv.) and DIEA (5.21 mL, 30 mmol, 3.0 equiv.) in sequence. The reaction was completed in 15 min. Ether (100 mL) and brine (100 mL) were added to the reaction mixture. The organic layer was dried and concentrated. The residue was purified on silica gel column using a mixture of hexane and EtOAc to give (S)-tert-butyl 4-(5-(tert-butyldimethylsilyloxy)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)pentanoyl)piperazine-1-carboxylate (4.2 g, 68%). LRMS (M+H+) m/z 615.2.

Workup

  1. customThe organic layer was dried
  2. concentrationconcentrated
  3. customThe residue was purified on silica gel column
  4. additiona mixture of hexane and EtOAc

Sources & evidence

ORD record
ord-77f440f852d749f19de0389e7ec9d4d6
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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