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 1751411ノート

反応式

HRID 1751411 の反応式
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]

参加物

7

反応物 5

HCID 313Hydrochloric Acid2 回HCID 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

生成物 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 ester収率 12.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e07e3f3d7f0a4e7b9f10dc85315125a6
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…