Diisopropylethylamine → HCID 178502121, 화합물

HRID 1625493

반응식

HRID 1625493 반응식
[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]

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 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

생성물 1

HCID 178502121HCID 178502121, 화합물수율 42.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 516892Sodium Bicarbonate용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-b843837a9b0c4569b8e57437bcbba786
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08779156B2

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