Diisopropylcarbodiimide → (R)-3-((5-(4-chlorophenyl)-1-ethyl-4-(3-(4-(4-(4-((4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-2-methyl-1H-pyrrole-3-carbonyl)oxy)propanoic acid

HRID 510809노트

반응식

HRID 510809 반응식
CC(C)N=C=NC(C)C.O[CH2:11][CH2:12][C:13]([O:15]C(C)(C)C)=[O:14].[CH3:20][CH2:21][N:22]1[C:26]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)=[C:25]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([N:40]3[CH2:45][CH2:44][N:43]([C:46]4[CH:51]=[CH:50][C:49]([NH:52][S:53]([C:56]5[CH:61]=[CH:60][C:59]([NH:62][C@@H:63]([CH2:73][S:74][C:75]6[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=6)[CH2:64][CH2:65][N:66]6[CH2:71][CH2:70][CH:69]([OH:72])[CH2:68][CH2:67]6)=[C:58]([S:81]([C:84]([F:87])([F:86])[F:85])(=[O:83])=[O:82])[CH:57]=5)(=[O:55])=[O:54])=[CH:48][CH:47]=4)[CH2:42][CH2:41]3)[CH:35]=2)[C:24]([C:88]([OH:90])=[O:89])=[C:23]1[CH3:91]>CN(C1C=CN=CC=1)C.C(Cl)Cl.C(OCC)(=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C:26]2[N:22]([CH2:21][CH3:20])[C:23]([CH3:91])=[C:24]([C:88]([O:90][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:89])[C:25]=2[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([N:40]3[CH2:41][CH2:42][N:43]([C:46]4[CH:47]=[CH:48][C:49]([NH:52][S:53]([C:56]5[CH:61]=[CH:60][C:59]([NH:62][C@H:63]([CH2:64][CH2:65][N:66]6[CH2:67][CH2:68][CH:69]([OH:72])[CH2:70][CH2:71]6)[CH2:73][S:74][C:75]6[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=6)=[C:58]([S:81]([C:84]([F:85])([F:86])[F:87])(=[O:82])=[O:83])[CH:57]=5)(=[O:55])=[O:54])=[CH:50][CH:51]=4)[CH2:44][CH2:45]3)[CH:35]=2)=[CH:28][CH:29]=1

참가 물질

7

반응물 3

HCID 12734DiisopropylcarbodiimideHCID 16218743tert-Butyl 3-hydroxypropanoateHCID 71456995HCID 71456995, 화합물

생성물 1

HCID 90279380(R)-3-((5-(4-chlorophenyl)-1-ethyl-4-(3-(4-(4-(4-((4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-2-methyl-1H-pyrrole-3-carbonyl)oxy)propanoic acid수율 70%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 957 (100 mg, 0.09 mmol), DIC (18 mg, 0.14 mmol) and DMAP (20 mg, 0.14 mmol) in DCM (2 mL) was added tert-butyl 3-hydroxypropanoate (41 mg, 0.28 mmol). The solution was stirred for 6 hours at room temperature until no BM-957 was observed by TLC. The reaction mixture was diluted with ethyl acetate (50 mL), washed with saturated NaHCO3 solution (50 mL), brine (50 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give crude product which was used for next step without purification. The resulting residue was dissolved in DCM (5 mL) and followed by adding TFA (2.5 mL). The solution was stirred at room temperature for 3 h until no starting material was observed by TLC. The reaction mixture was concentrated in vacuo and the residue was purified by HPLC to give the pure product 5 (salt with TFA, 75 mg, yield 70% over two steps). The gradient ran from 60% of solvent A and 40% of solvent B to 20% of solvent A and 80% of solvent B in 40 min. MS (ESI): m/z 1238.17 (M+H)+.

후처리

  1. washwashed with saturated NaHCO3 solution (50 mL), brine (50 mL)
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed in vacuo
  4. customto give crude product which
  5. customwas used for next step without purification
  6. dissolutionThe resulting residue was dissolved in DCM (5 mL)
  7. additionby adding TFA (2.5 mL)
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. customthe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-d2812abd015f463ab8884e76f706f327
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096625B2

반응 노트

불러오는 중…