Dimethylformamide → 4-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyrylamino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 511123노트

반응식

HRID 511123 반응식
[Li+].F[C:3](F)(F)[C:4]1[CH:9]=CC(N2CCN(CCCC([O-])=O)CC2)=C[CH:5]=1.F[P-](F)(F)(F)(F)F.CN(C)C([O:37]N1C2C=CC=CC=2N=N1)=[N+](C)C.[N+](C1C=CC(N2C[CH2:61][CH:60]([NH:63][C:64](=[O:84])[CH2:65][CH2:66][CH2:67][N:68]3[CH2:73][CH2:72][N:71]([C:74]4[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:82])[F:81])=[CH:76][CH:75]=4)[CH2:70][CH2:69]3)[CH2:59]C2)=CC=1C(F)(F)F)([O-])=O.C(N(C(C)C)CC)(C)C.[CH3:98][N:99]([CH3:102])[CH:100]=[O:101]>C(OC(=O)C)C.O1CCCC1>[C:4]([O:101][C:100]([N:99]1[CH2:102][CH2:61][CH:60]([NH:63][C:64](=[O:84])[CH2:65][CH2:66][CH2:67][N:68]2[CH2:73][CH2:72][N:71]([C:74]3[CH:79]=[CH:78][C:77]([C:80]([F:83])([F:81])[F:82])=[CH:76][CH:75]=3)[CH2:70][CH2:69]2)[CH2:59][CH2:98]1)=[O:37])([CH3:9])([CH3:5])[CH3:3]

참가 물질

8

반응물 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585760704-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 58576694N-[1-(4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl]-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-butyramide2회

생성물 1

HCID 585766414-{4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyrylamino}-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (425 mg; 1.32 mmol, prepared in accordance with Example 3) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (500 mg; 1.32 mmol) are diluted in a 5 to 1 mixture of dimethylformamide and tetrahydrofuran (6 mL) and the resulting solution is stirred for 5 minutes. 4-Amino-piperidine-1-carboxylic acid tert-butyl ester (264 mg; 1.32 mmol, free base of Example 73) and diisopropylethyl amine (460 μL; 2.64 mmol) are added and the reaction is then stirred for 90 minutes at room temperature. Following dilution with ethylacetate (30 mL), the organic layer is washed with aq. sat. sodium hydrogen carbonate (3×10 mL), is dried over magnesium sulfate and concentrated under reduced pressure to afford the desired product (660 mg; 1.32 mmol).

후처리

  1. stirringthe reaction is then stirred for 90 minutes at room temperature
  2. washthe organic layer is washed with aq. sat. sodium hydrogen carbonate (3×10 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-be0038d5de9f423fa4f37813b07fa2d7
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096524B2

반응 노트

불러오는 중…