Diisopropylethylamine → HCID 178502431, 화합물

HRID 1625496

반응식

HRID 1625496 반응식
Cl.[CH3:2][O:3][C:4](=[O:51])[N:5](C)[C@H:6]([C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][NH:45]6)[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:29][CH:28]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])[CH:7]([CH3:9])[CH3:8].[CH3:52][O:53][C:54]([N:56]([CH3:64])[C@@H:57]([CH:61]([CH3:63])[CH3:62])[C:58]([OH:60])=O)=[O:55].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>CN(C=O)C.O>[CH3:2][O:3][C:4]([NH:5][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C:10]([N:12]1[CH2:16][C@@H:15]([CH3:17])[CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([C:27]3[CH:28]=[CH:29][C:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]5[N:40]=[C:41]([C@@H:44]6[CH2:48][C@H:47]([CH3:49])[CH2:46][N:45]6[C:58](=[O:60])[C@@H:57]([N:56]([CH3:64])[C:54](=[O:55])[O:53][CH3:52])[CH:61]([CH3:63])[CH3:62])[NH:42][CH:43]=5)=[CH:35][CH:34]=4)=[CH:31][CH:32]=3)=[CH:26][C:20]=2[N:19]=1)=[O:11])=[O:51]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59166373N-(Methoxycarbonyl)-N-methyl-L-valineHCID 178502120HCID 178502120, 화합물

생성물 1

HCID 178502431HCID 178502431, 화합물수율 43.9%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of methyl {(S)-2-methyl-1-[(2S,4S)-4-methyl-2-(5-{4′-[2-((2S,4S)-4-methyl-pyrrolidin-2-yl)-1H-imidazol-4-yl]-biphenyl-4-yl}-1H-benzoimidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester hydrochloride (68.7 mg, 0.0987 mmol) and (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (18.67 mg, 0.09867 mmol) in DMF (2 mL), cooled in an ice bath is sequentially added HATU (41.25 mg, 0.1085 mmol) and DIPEA (38.26 mg, 51.56 μL, 0.2960 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 5 hours, and diluted with water (6 mL). The mixture is extracted with EtOAc (5×6 mL), and the combined organic layers are washed with H2O (3×3 mL), dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2) and is further purified by reverse phase preparative HPLC to give methyl ((S)-1-((2S,4S)-2-(4-(4′-(2-((2S,4S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-4-methylpyrrolidin-2-yl)-3H-benzo[d]imidazol-6-yl)-[1,1′-biphenyl]-4-yl)-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)(methyl)carbamate (36 mg, 41%).

후처리

  1. extractionThe mixture is extracted with EtOAc (5×6 mL)
  2. washthe combined organic layers are washed with H2O (3×3 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe residue is purified by flash column chromatography on silica gel (0 to 10% methanol in CH2Cl2)
  7. customis further purified by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-acbcc9b13f2a422bb0a069f0ad4f06a1
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

연결된 노트

불러오는 중…