Hydrochloric Acid → HCID 178495651, 화합물

HRID 1509673노트

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HRID 1509673 반응식
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]1[NH:20][C:19]2[C:21]3[C:26]([CH:27]=[CH:28][C:18]=2[N:17]=1)=[CH:25][C:24]1[C:29]2[C:34]([CH2:35][O:36][C:23]=1[CH:22]=3)=[CH:33][C:32]([C:37]1[CH:38]=[CH:39][C:40]3[N:44]=[C:43]([C@@H:45]4[CH2:49][CH2:48][CH2:47][N:46]4[C:50](=[O:60])[C@@H:51]([NH:55][C:56]([O:58][CH3:59])=[O:57])[CH:52]([CH3:54])[CH3:53])[NH:42][C:41]=3[CH:61]=1)=[CH:31][CH:30]=2)=O)(C)(C)C.Cl.[CH3:63][O:64][C:65]([NH:67][C@@H:68]([CH:72]([CH3:74])[CH3:73])[C:69](O)=[O:70])=[O:66].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C.C(O)C>[CH3:59][O:58][C:56]([NH:55][C@@H:51]([CH:52]([CH3:53])[CH3:54])[C:50]([N:46]1[CH2:47][CH2:48][CH2:49][C@H:45]1[C:43]1[NH:42][C:41]2[CH:61]=[C:37]([C:32]3[CH:33]=[C:34]4[CH2:35][O:36][C:23]5[CH:22]=[C:21]6[C:26]([CH:27]=[CH:28][C:18]7[N:17]=[C:16]([C@@H:9]8[CH2:10][C@H:11]([CH2:13][O:14][CH3:15])[CH2:12][N:8]8[C@@:68]([NH:67][C:65](=[O:66])[O:64][CH3:63])([CH:72]([CH3:74])[CH3:73])[CH:69]=[O:70])[NH:20][C:19]=76)=[CH:25][C:24]=5[C:29]4=[CH:30][CH:31]=3)[CH:38]=[CH:39][C:40]=2[N:44]=1)=[O:60])=[O:57]

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178495652HCID 178495652, 화합물

생성물 1

HCID 178495651HCID 178495651, 화합물수율 40%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (2S,4S)-tert-butyl-2-(9-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (156 mg, 0.18 mmol), ethanol (3 mL) and concentrated HCl (1 mL) was heated to 60° C. for 1 hour. The reaction was concentrated and the crude material dissolved in DCM (6 mL). This solution was concentrated and to 68 mg (0.09 mmol) of this material was added a solution of (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (21 mg, 0.12 mmol) and HATU (41 mg, 0.1 mmol) in DMF (1 mL). To the resulting solution was added diisopropylethylamine (50 L, 0.28 mmol). After stirring for 2 hours at room temperature, the reaction was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), concentrated and purified by preparative reverse phase HPLC (Gemini, 15 to 44% ACN/H2O+0.1% TFA). The product fractions were lyophilized to give methyl {(2S)-2-[(2S,4S)-2-{9-[2-((2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-y]-1,11-dihydroisochrome no[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl}-4-(methoxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (32 mg, 40%). MS (ESI) m/z 886 [M+H]+.

후처리

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DCM (6 mL)
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by preparative reverse phase HPLC (Gemini, 15 to 44% ACN/H2O+0.1% TFA)

출처 및 근거

ORD 기록
ord-9dddbe5f340e494abeefd46a0b4a8bf3
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221833B2

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