Diisopropylethylamine → HCID 178455974、化合物

HRID 1431882ノート

反応式

HRID 1431882 の反応式
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([N:13]1[CH2:17][C@@H:16]([CH3:18])[CH2:15][C@H:14]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[C:28]3[CH2:30][O:31][C:32]4[CH:59]=[C:58]5[C:35]([CH:36]=[CH:37][C:38]6[N:42]=[C:41]([C@@H:43]7[CH2:47][C@H:46]([CH2:48][O:49][CH3:50])[CH2:45][N:44]7[C:51](OC(C)(C)C)=[O:52])[NH:40][C:39]=65)=[CH:34][C:33]=4[C:27]3=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:12])[C@@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4].[CH3:60][O:61][C:62]([NH:64][C@H:65]([C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)C(O)=O)=[O:63].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>Cl.CCO>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([C@H:7]([CH3:8])[CH2:9][CH3:10])[C:11]([N:13]1[CH2:17][C@@H:16]([CH3:18])[CH2:15][C@H:14]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[C:28]3[CH2:30][O:31][C:32]4[CH:59]=[C:58]5[C:35]([CH:36]=[CH:37][C:38]6[N:42]=[C:41]([C@@H:43]7[CH2:47][C@H:46]([CH2:48][O:49][CH3:50])[CH2:45][N:44]7[C:51](=[O:52])[C@H:65]([NH:64][C:62](=[O:63])[O:61][CH3:60])[C:69]7[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=7)[NH:40][C:39]=65)=[CH:34][C:33]=4[C:27]3=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:12])=[O:4]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 10910775(alphaR)-alpha-((Methoxycarbonyl)amino)benzeneacetic acidHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphateHCID 178455977HCID 178455977、化合物

生成物 1

HCID 178455974HCID 178455974、化合物収率 50%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 702Ethanol溶媒

実験手順

A solution of tert-butyl (2S,4S)-2-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-alloisoleucyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (218 mg, 0.27 mmol) in 1.25 N HCl in EtOH (3 mL) was heated to 50° C. for 3 h. The reaction was concentrated and the crude material dissolved in DMF (3 mL). To this solution was added a solution of (R)-2-(methoxycarbonylamino)-2-phenylacetic acid (73 mg, 0.35 mmol) and COMU (127 mg, 0.30 mmol). To the resulting solution was added diisopropylethylamine (0.141 mL, 0.81 mmol). After stirring for 2 h at room temperature, the reaction was quenched with 1N HCl (0.200 mL) and purified by HPLC. After lyophilization, the TFA salt was dissolved in EtOAc and washed with saturated NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The free base was then dissolved in MeCN/H2O and lyophilized to afford methyl {(1R)-2-[(2S,4S)-2-(9-{2-[(2S,4S)-1-{(2S,3R)-2-[(methoxycarbonyl)amino]-3-methylpentanoyl}-4-methylpyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl}carbamate (121 mg, 50%). LCMS-ESI+: calculated for C50H56N8O8: 896.4; observed [M+1]+: 897.5.

後処理

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DMF (3 mL)
  3. customthe reaction was quenched with 1N HCl (0.200 mL)
  4. custompurified by HPLC
  5. dissolutionAfter lyophilization, the TFA salt was dissolved in EtOAc
  6. washwashed with saturated NaHCO3
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated
  9. dissolutionThe free base was then dissolved in MeCN/H2O

出典と根拠

ORDレコード
ord-d2257c6a15684757a8bd3b967e7a3def
出典データセット
uspto-grants-2015_01
特許番号
US08940718B2

反応ノート

読み込み中…