3-[1-(5-Methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester → HCID 178425540, compound

HRID 1045051Notes

Reaction equation

HRID 1045051 reaction equation
[C:1]([O:5][C:6](=[O:20])[CH2:7][CH2:8][N:9]([CH2:13][C:14]1[S:15][C:16]([CH3:19])=[CH:17][CH:18]=1)[C:10]([NH2:12])=[S:11])([CH3:4])([CH3:3])[CH3:2].Br[CH2:22][C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26]1)=O>CO>[C:1]([O:5][C:6](=[O:20])[CH2:7][CH2:8][N:9]([C:10]1[S:11][CH:22]=[C:23]([C@H:25]2[CH2:26][CH2:27][C@H:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:29][CH2:30]2)[N:12]=1)[CH2:13][C:14]1[S:15][C:16]([CH3:19])=[CH:17][CH:18]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 592267123-[1-(5-Methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl esterHCID 178445648HCID 178445648, compound

Product 1

HCID 178425540HCID 178425540, compoundYield 104.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-[1-(5-methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (100 mg, 0.318 mmol) in MeOH (about 4 mL) was treated with two portions of 2-Bromo-1-(trans-4-tert-butyl-cyclohexyl)-ethanone (2×83 mg, 2×0.318 mmol) (second addition spaced at an interval of 2 hours after first portion) at 60° C. following a method analogous to General Procedure C to produce 3-[[4-(trans-4-tert-Butyl-cyclohexyl)-thiazol-2-yl]-(5-methyl-thiophen-2-ylmethyl)-amino]propionic acid tert-butyl ester (158 mg). which was isolated by a workup that included evaporation of the solvent and partitioning the resulting material between EtOAc and saturated aq sodium bicarbonate solution. Extraction of the aq sodium bicarbonate layer with EtOAc (2 times), drying the combined organic portion over sodium sulfate and evaporation of the solvent gave the crude material which was purified using silica gel chromatography (eluent hexanes→19:1 ethyl acetate:hexanes→9:1 ethyl acetate:hexanes).

Workup

  1. additionsecond addition
  2. customspaced at an interval of 2 hours
  3. customat 60° C.

Sources & evidence

ORD record
ord-d7fdb2a4f181430da241e2dc8c87d9bb
Source dataset
uspto-grants-2013_10
Patent number
US08563742B2

Reaction notes

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