Diisopropylethylamine → HCID 178499337, compound

HRID 1614907Notes

Reaction equation

COC(C1SC(C#CC(C)(C)C)=CC=1NC1CC(OCC2C=CC=CC=2)C1)=O.C(N(CC)C(C)C)(C)C.C[C@H]1CC[C@H](C(Cl)=O)CC1.[CH3:48][O:49][C:50]([C:52]1[S:53][C:54]([C:79]#[C:80][C:81]([CH3:84])([CH3:83])[CH3:82])=[CH:55][C:56]=1[N:57]([CH:67]1[CH2:70][CH:69]([O:71][CH2:72][C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)[CH2:68]1)[C:58]([C@H:60]1[CH2:65][CH2:64][C@H:63]([CH3:66])[CH2:62][CH2:61]1)=[O:59])=[O:51]>ClCCCl>[CH3:48][O:49][C:50]([C:52]1[S:53][C:54]([C:79]#[C:80][C:81]([CH3:82])([CH3:84])[CH3:83])=[CH:55][C:56]=1[N:57]([CH:67]1[CH2:70][CH:69]([O:71][CH2:72][C:73]2[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=2)[CH2:68]1)[C:58]([C@H:60]1[CH2:65][CH2:64][C@@H:63]([CH3:66])[CH2:62][CH2:61]1)=[O:59])=[O:51]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-(3-Benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (1.26 g, 3.17 mmol) and N,N-diisopropylethylamine (2.4 mL, 13.8 mmol) in DCE (8 mL) was treated with trans-4-methyl-cyclohexanecarbonyl chloride and heated to 100° C. for 5 hours. The reaction mixture was cooled to room temperature, adsorbed onto silica, and purified by silica gel chromatography (0-30% ethyl acetate:hexanes). This resulted in 590 mg (36% yield) of cis-cyclobutyl isomer (cis-3-[(3-benzyloxy-cyclobutyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester) and 230 mg (14% yield) of the trans-cyclobutyl isomer (trans-3-[(3-benzyloxy-cyclobutyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester).

Workup

temperatureThe reaction mixture was cooled to room temperature
custompurified by silica gel chromatography (0-30% ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-29799bc22e1147ee93d830ce75c64fd6
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765722B2

Reaction notes

Loading…