4-Methylmorpholine → (1-{1-[2-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-2-oxo-ethylcarbamoyl]-ethyl}-2-oxo-piperidin-3-yl)-carbamic acid methyl ester

HRID 79710

반응식

HRID 79710 반응식
[CH3:1][O:2][C:3]([NH:5][CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH:12]([CH3:16])[C:13]([OH:15])=O)[C:7]1=[O:17])=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:49][O:50][C:51](=[O:85])[NH:52][CH:53]([C:57]([N:59]1[CH2:63][CH2:62][CH2:61][CH:60]1[C:64]1[NH:65][C:66]([C:69]2[CH:74]=[CH:73][C:72]([C:75]3[CH:80]=[CH:79][C:78]([C:81](=[O:84])[CH2:82][NH2:83])=[CH:77][CH:76]=3)=[CH:71][CH:70]=2)=[CH:67][N:68]=1)=[O:58])[CH:54]([CH3:56])[CH3:55]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH:12]([C:13](=[O:15])[NH:83][CH2:82][C:81]([C:78]2[CH:79]=[CH:80][C:75]([C:72]3[CH:71]=[CH:70][C:69]([C:66]4[NH:65][C:64]([CH:60]5[CH2:61][CH2:62][CH2:63][N:59]5[C:57](=[O:58])[CH:53]([NH:52][C:51]([O:50][CH3:49])=[O:85])[CH:54]([CH3:56])[CH3:55])=[N:68][CH:67]=4)=[CH:74][CH:73]=3)=[CH:76][CH:77]=2)=[O:84])[CH3:16])[C:7]1=[O:17]

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66620889[1-(2-{5-[4'-(2-Amino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterHCID 666210692-(3-Methoxycarbonylamino-2-oxo-piperidin-1-yl)-propionic acid

생성물 1

HCID 66620876(1-{1-[2-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-2-oxo-ethylcarbamoyl]-ethyl}-2-oxo-piperidin-3-yl)-carbamic acid methyl ester수율 100%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 2-(3-methoxycarbonylamino-2-oxo-piperidin-1-yl)-propionic acid (48.5 mg, 0.20 mmol), HATU (91 mg, 0.24 mmol), and 4-methylmorpholine (109 μL, 0.99 mmol) in dimethylformamide (5 mL) was stirred at ambient temperature for 5 minutes. [1-(2-{5-[4′-(2-Amino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (100 mg, 0.20 mmol) was added to the reaction mixture. After 40 minutes the solvent was removed under reduced pressure and the resulting residue was taken up in ethyl acetate (10 mL). The resulting mixture contained a solid and was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane followed by 30% methanol in DCM. The product-containing fractions were combined and the solvent was removed under reduced pressure to provide (1-{1-[2-(4′-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-2-oxo-ethylcarbamoyl]-ethyl}-2-oxo-piperidin-3-yl)-carbamic acid methyl ester (149 mg, 0.20 mmol, 99%). C38H47N7O8 calculated 729.4 observed [M+1]+ 730.6; rt=1.78 min.

후처리

  1. customAfter 40 minutes the solvent was removed under reduced pressure
  2. customthe solvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-1d408630effd44d3bc81f157802fa03d
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841278B2

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