Diisopropylethylamine → {4-[2-(3,3-Dicyclohexyl-ureido)-thiazole-5-carbonyl]-piperazin-1-yl}-acetic acid ethyl ester

HRID 1818362Notes

Reaction equation

HRID 1818362 reaction equation
[CH:1]1([N:7]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:8](=[O:18])[NH:9][C:10]2[S:11][C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1([C:31](=[O:39])[CH2:32][N:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)CCOCC1.CN(C([O:47]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN([CH:70]([CH3:72])C)C(C)C>CCOC(C)=O.CN(C=O)C>[CH2:70]([O:47][C:31](=[O:39])[CH2:32][N:33]1[CH2:34][CH2:35][N:36]([C:15]([C:12]2[S:11][C:10]([NH:9][C:8]([N:7]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]3)[CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:18])=[N:14][CH:13]=2)=[O:17])[CH2:37][CH2:38]1)[CH3:72]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1006221-(Morpholinocarbonylmethyl)piperazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114054472-(3,3-Dicyclohexylureido)thiazole-5-carboxylic acid

Product 1

HCID 57883964{4-[2-(3,3-Dicyclohexyl-ureido)-thiazole-5-carbonyl]-piperazin-1-yl}-acetic acid ethyl esterYield 49%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(3,3-Dicyclohexyl-ureido)-thiazole-5-carboxylic acid (53 mg, 0.15 mmol), 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (39 mg, 0.23 mmol), and HBTU (74 mg, 0.19 mmol) were weighed out and added to a 25 mL reaction flask. DMF (2 mL) and DIEA (52 μL, 0.30 mmol) were added. The reaction was stirred under nitrogen at ambient temperature overnight. The reaction was diluted with EtOAc (10 mL) and quenched with saturated aqueous NH4Cl (10 mL). After separation and extraction with EtOAc (2×5 mL) the combined organic portions were dried over MgSO4. Purification with silica gel chromatography (10% EtOAc and 1% MeOH in CH2Cl2) afforded 37 mg (49%) of the desired compound.

Workup

  1. additionadded to a 25 mL reaction flask
  2. customquenched with saturated aqueous NH4Cl (10 mL)
  3. customAfter separation and extraction with EtOAc (2×5 mL) the combined organic portions
  4. dry with materialwere dried over MgSO4
  5. customPurification with silica gel chromatography (10% EtOAc and 1% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-bc2111bd1d8b4cd688efe80c7a206859
Source dataset
uspto-grants-2009_10
Patent number
US07598391B2

Reaction notes

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