Dicyclohexylamine → [2-(3,3-Dicyclohexyl-ureido)-thiazole-5-sulfonylamino]-acetic acid ethyl ester

HRID 731444Notes

Reaction equation

HRID 731444 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][NH:6][S:7]([C:10]1[S:14][C:13]([NH2:15])=[N:12][CH:11]=1)(=[O:9])=[O:8])[CH3:2].[CH:17]1([NH:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C1C[O:33][CH2:32]C1>CN(C1C=CN=CC=1)C>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][NH:6][S:7]([C:10]1[S:14][C:13]([NH:15][C:32]([N:23]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)[CH:24]2[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]2)=[O:33])=[N:12][CH:11]=1)(=[O:8])=[O:9])[CH3:2]

Participants

5

Reactant 3

HCID 7582DicyclohexylamineHCID 8028TetrahydrofuranHCID 86253773(2-Amino-thiazole-5-sulfonylamino)acetic acid ethyl ester

Product 1

HCID 86630192[2-(3,3-Dicyclohexyl-ureido)-thiazole-5-sulfonylamino]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Conditions

Temperature
55 °C

Procedure

An equimolar mixture of 1,1-carbonyldiimidazole, (2-amino-thiazole-5-sulfonylamino)-acetic acid ethyl ester and DMAP (5 mol %) in THF was heated for 2 h at 50-60° C. and then cooled to room temperature. Then dicyclohexylamine (1 equivalent) was added and the reaction is stirred overnight at room temperature. The reaction mixture was quenched with water. The organic phase was isolated and the aqueous phase was extracted with CH2Cl2, and the combined organic phases were dried and concentrated in vacuo. The crude product was dissolved in MeCN and purified (HPLC method 1) to give [2-(3,3-dicyclohexyl-ureido)-thiazole-5-sulfonylamino]-acetic acid ethyl ester. This material was dissolved in MeOH and treated with 20 equivalents of 1N NaOH over night at room temperature. MeOH was removed by evaporation. Addition of 1N HCl to pH<1 caused precipitation. The precipitate was isolated by filtration, washed with water and dried to give title compound.

Workup

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was quenched with water
  3. customThe organic phase was isolated
  4. extractionthe aqueous phase was extracted with CH2Cl2
  5. customthe combined organic phases were dried
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude product was dissolved in MeCN
  8. custompurified (HPLC method 1)

Sources & evidence

ORD record
ord-940d88370f714432b453864ad357bd96
Source dataset
uspto-grants-2009_09
Patent number
US07582769B2

Reaction notes

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