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ノート

反応式

HRID 79710 の反応式
[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]

参加物

6

反応物 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

生成物 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 ester収率 100%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-1d408630effd44d3bc81f157802fa03d
出典データセット
uspto-grants-2014_09
特許番号
US08841278B2

反応ノート

読み込み中…