Hydrochloric Acid → HCID 178495651、化合物

HRID 1751638ノート

反応式

HRID 1751638 の反応式
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]([C:72]1[CH:77]=CC=C[CH:73]=1)[C:69](O)=[O:70])=[O:66].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.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]([CH3:77])[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]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178495652HCID 178495652、化合物

生成物 1

HCID 178495651HCID 178495651、化合物収率 40%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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 (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (21 mg, 0.12 mmol) and COMU (41 mg, 01 mmol) in DMF (1 mL). To the resulting solution was added diisopropylethylamine (50 μL, 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-yl]-1,11-dihydroisochromeno[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]f.

後処理

  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)

出典と根拠

ORDレコード
ord-0a0b92f2413e4c2792fcaa259d8a0434
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…