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Acetic Acid → (R)-4-[5-[[2-[[tert-Butyldimethylsilyl)oxy]-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pentyl]-N-[[1,6-diethyl-4-[(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl]benzamide

HRID 385273
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HRID 385273 반응식
[BH3-]C#N.[Na+].[NH2:5][CH2:6][C@@H:7]([C:16]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]2[C:17]=1[CH:18]=[CH:19][C:20](=[O:27])[NH:21]2)[O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].[CH2:28]([N:30]1[C:34]2=[N:35][C:36]([CH2:62][CH3:63])=[C:37]([CH2:46][NH:47][C:48](=[O:61])[C:49]3[CH:54]=[CH:53][C:52]([CH2:55][CH2:56][CH2:57][CH2:58][CH:59]=O)=[CH:51][CH:50]=3)[C:38]([NH:39][CH:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[C:33]2[CH:32]=[N:31]1)[CH3:29].C(O)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O.O>[Si:9]([O:8][C@H:7]([C:16]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]2[C:17]=1[CH:18]=[CH:19][C:20](=[O:27])[NH:21]2)[CH2:6][NH:5][CH2:59][CH2:58][CH2:57][CH2:56][CH2:55][C:52]1[CH:51]=[CH:50][C:49]([C:48]([NH:47][CH2:46][C:37]2[C:38]([NH:39][CH:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)=[C:33]3[CH:32]=[N:31][N:30]([CH2:28][CH3:29])[C:34]3=[N:35][C:36]=2[CH2:62][CH3:63])=[O:61])=[CH:54][CH:53]=1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 58505298N-[[1,6-Diethyl-4-[(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl]-4-(5-oxopentyl)benzamideHCID 59023604(R)-5-(2-Amino-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-hydroxyquinolin-2(1H)-one

생성물 1

HCID 66989901
(R)-4-[5-[[2-[[tert-Butyldimethylsilyl)oxy]-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pentyl]-N-[[1,6-diethyl-4-[(tetrahydro-2H-pyran-4-yl)amino]-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl]benzamide
수율 48.4%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

NaCNBH3 (160 mg, 2.55 mmol) was added to a solution of Intermediate 2 (240 mg, 0.61 mmol), Intermediate 36 (250 mg, 0.51 mmol), and acetic acid (0.032 mL, 0.561 mmol) in THF (5 mL). The reaction mixture was stirred at rt for 1 h. H2O (2 mL) was added followed by satd. NaHCO3 solution (20 mL) and EtOAc (100 mL). The organic layer was separated, dried over MgSO4 (s), filtered, and concentrated in vacuo. Purification by column chromatography on silica gel eluting with a gradient of 0-100% DCM-DCM/MeOH/Ammonia (80/20/1) afforded the title compound as a yellow solid (200 mg). ES/MS calcd. for C45H64N7O5Si+ 810.5. found m/z=810.5 (M+H)+.

후처리

  1. customThe organic layer was separated
  2. dry with materialdried over MgSO4 (s)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography on silica gel eluting with a gradient of 0-100% DCM-DCM/MeOH/Ammonia (80/20/1)

출처 및 근거

ORD 기록
ord-1893edecbe03499791c6acf338fad33a
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08367829B2

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