Diisopropylethylamine → HCID 178502121、化合物

HRID 1625493ノート

反応式

HRID 1625493 の反応式
[CH3:1][O:2][C:3]([N:5]([CH3:13])[C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7](O)=[O:8])=[O:4].Cl.[CH3:15][N:16]([C@@H:21]([CH:62]([CH3:64])[CH3:63])[C:22]([N:24]1[CH2:28][C@@H:27]([CH3:29])[CH2:26][C@H:25]1[C:30]1[NH:34][C:33]2[CH:35]=[C:36]([C:39]3[CH:44]=[CH:43][C:42]([C:45]4[CH:50]=[CH:49][C:48]([C:51]5[NH:55][C:54]([C@@H:56]6[CH2:60][C@H:59]([CH3:61])[CH2:58][NH:57]6)=[N:53][CH:52]=5)=[CH:47][CH:46]=4)=[CH:41][CH:40]=3)[CH:37]=[CH:38][C:32]=2[N:31]=1)=[O:23])[C:17](=[O:20])[O:18][CH3:19].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.C([O-])(O)=O.[Na+]>[CH3:19][O:18][C:17]([N:16]([CH3:15])[C@@H:21]([CH:62]([CH3:64])[CH3:63])[C:22]([N:24]1[CH2:28][C@@H:27]([CH3:29])[CH2:26][C@H:25]1[C:30]1[NH:31][C:32]2[CH:38]=[CH:37][C:36]([C:39]3[CH:40]=[CH:41][C:42]([C:45]4[CH:50]=[CH:49][C:48]([C:51]5[N:55]=[C:54]([C@@H:56]6[CH2:60][C@H:59]([CH3:61])[CH2:58][N:57]6[C:7]([C@@H:6]([N:5]([CH3:13])[C:3](=[O:4])[O:2][CH3:1])[CH:10]([CH3:12])[CH3:11])=[O:8])[NH:53][CH:52]=5)=[CH:47][CH:46]=4)=[CH:43][CH:44]=3)=[CH:35][C:33]=2[N:34]=1)=[O:23])=[O:20]

参加物

7

反応物 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 67413654Methyl-{(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

生成物 1

HCID 178502121HCID 178502121、化合物収率 42.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

To a solution of (2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoic acid (12.8 mg, 0.06765 mmol) and methyl methyl((S)-3-methyl-1-((2S,4S)-4-methyl-2-(6-(4′-(2-((2S,4S)-4-methylpyrrolidin-2-yl)-1H-imidazol-5-yl)[1,1′-biphenyl]-4-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-1-oxobutan-2-yl)carbamate hydrochloride (48.1 mg, 0.0677 mmol) in DMF (2 mL) cooled in an ice bath is sequentially added HATU (28.3 mg, 0.0744 mmol) and DIPEA (0.035 mL, 0.203 mmol) under nitrogen atmosphere. The reaction mixture is stirred at room temperature for 19 hours and diluted with saturated aqueous NaHCO3 (2 mL). The mixture is extracted with EtOAc (5×3 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 reverse phase preparative HPLC to give methyl N-[(1S)-1-[(2S,4S)-2-[4-[4-[4-[2-[(2S,4S)-1-[(2S)-2-[methoxycarbonyl(methyl)amino]-3-methyl-butanoyl]-4-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-4-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]-N-methyl-carbamate (24.4 mg, 41%).

後処理

  1. extractionThe mixture is extracted with EtOAc (5×3 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 reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-b843837a9b0c4569b8e57437bcbba786
出典データセット
uspto-grants-2014_07
特許番号
US08779156B2

反応ノート

読み込み中…