Hydrochloric Acid → {2-[2-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-4-methylene-pyrrolidin-1-yl]-2-oxo-1-pyridin-3-yl-ethyl}-carbamic acid methyl ester

HRID 1751411노트

반응식

HRID 1751411 반응식
C(OC([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][CH:9]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[C:30]([C:35]5[NH:36][C:37]([CH:40]6[CH2:44][CH2:43][CH2:42][N:41]6[C:45](=[O:58])[CH:46]([NH:53][C:54]([O:56][CH3:57])=[O:55])[CH:47]6[CH2:52][CH2:51][O:50][CH2:49][CH2:48]6)=[N:38][CH:39]=5)[CH:31]=4)[CH:26]=3)=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=O)(C)(C)C.Cl.[CH3:60][O:61][C:62]([NH:64][CH:65]([C:69]1[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=1)[C:66]([OH:68])=O)=[O:63].[Na+].[Cl-].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:60][O:61][C:62](=[O:63])[NH:64][CH:65]([C:69]1[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=1)[C:66]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][CH:9]1[C:14]1[NH:15][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:34]=[CH:33][C:32]4[C:27](=[CH:28][CH:29]=[C:30]([C:35]5[NH:36][C:37]([CH:40]6[CH2:44][CH2:43][CH2:42][N:41]6[C:45](=[O:58])[CH:46]([NH:53][C:54]([O:56][CH3:57])=[O:55])[CH:47]6[CH2:52][CH2:51][O:50][CH2:49][CH2:48]6)=[N:38][CH:39]=5)[CH:31]=4)[CH:26]=3)=[CH:21][CH:20]=2)=[CH:17][N:18]=1)=[O:68]

참가 물질

7

반응물 5

HCID 313Hydrochloric Acid2회HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 696751812-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-4-methylene-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 131733615Methoxycarbonylamino-pyridin-3-yl-acetic acid NaCl

생성물 1

HCID 69675245{2-[2-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-4-methylene-pyrrolidin-1-yl]-2-oxo-1-pyridin-3-yl-ethyl}-carbamic acid methyl ester수율 12.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-(5-{4-[6-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-naphthalen-2-yl]-phenyl}-1H-imidazol-2-yl)-4-methylene-pyrrolidine-1-carboxylic acid tert-butyl ester (64 mg, 0.0816 mmol) was dissolved in DCM (1 mL) and HCl (4N dioxane, 1 mL) was added. After 20 minutes all volatiles were removed in vacuo. The crude material was dissolved in DMF (1 mL) and Methoxycarbonylamino-pyridin-3-yl-acetic acid/NaCl (1:1, 22 mg, 0.0816 mmol), HATU (31 mg, 0.0816 mmol), and DIEA (31.5 mg, 0.245 mmol) were added and stirring at room temperature was continued. After 30 minutes, aqueous HCl (1N, 0.1 mL) was added and the reaction mixture was purified via RP-HPLC (eluent: water/MeCN w/ 0.1% TFA). The product containing fractions were lyophilized to yield the product (8.9 mg).

후처리

  1. customAfter 20 minutes all volatiles were removed in vacuo
  2. dissolutionThe crude material was dissolved in DMF (1 mL)
  3. customthe reaction mixture was purified via RP-HPLC (eluent: water/MeCN w/ 0.1% TFA)
  4. additionThe product containing fractions

출처 및 근거

ORD 기록
ord-e07e3f3d7f0a4e7b9f10dc85315125a6
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

반응 노트

불러오는 중…