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Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486072
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HRID 1486072 반응식
[CH3:1][N:2]([C@@H:10]([CH3:35])[C:11]([NH:13][C@H:14]1[C@H:20]([CH3:21])[N:19]([C:22]([CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[O:23])[C:18]2[CH:30]=[CH:31][CH:32]=[CH:33][C:17]=2[NH:16][C:15]1=[O:34])=[O:12])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Br[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:40]([C:47]2[CH:54]=[CH:53][CH:52]=[CH:51][C:48]=2[C:49]#[N:50])[N:39]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[C:49]([C:48]1[CH:51]=[CH:52][CH:53]=[CH:54][C:47]=1[N:40]1[C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:38]([CH2:37][N:16]2[C:15](=[O:34])[C@@H:14]([NH:13][C:11](=[O:12])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8])[CH3:35])[C@H:20]([CH3:21])[N:19]([C:22]([CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[O:23])[C:18]3[CH:30]=[CH:31][CH:32]=[CH:33][C:17]2=3)=[N:39]1)#[N:50]
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참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 900376452-(3-Bromomethyl-indazol-1-yl)-benzonitrileHCID 90082481tert-butyl methyl((S)-1-((2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate

생성물 1

HCID 118292583
tert-butyl(S)-1-((3S,4S)-1-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate
수율 78.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a rt solution of tert-butyl methyl((S)-1-((2S,3S)-2-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl)carbamate (111 mg, 227 μmol) in DMF (568 μl) was added 2-(3-(bromomethyl)-1H-indazol-1-yl)benzonitrile (85.1 mg, 273 μmol), cesium carbonate (96.2 mg, 295 μmol), and sodium iodide (44.3 mg, 295 μmol). The reaction was stirred at rt for 2.5 days, then diluted with EtOAc, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((3S,4S)-1-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (128 mg, 78%) as an off-white solid. MS m/z 742 (MNa)+.

후처리

  1. washwashed with H2O and sat. aq. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography

출처 및 근거

ORD 기록
ord-61e4ec3d45844cc79cc977b98db3f1d3
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09422331B2

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