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 385273Notes

Reaction equation

HRID 385273 reaction equation
[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]

Participants

9

Reactant 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

Product 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]benzamideYield 48.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-1893edecbe03499791c6acf338fad33a
Source dataset
uspto-grants-2013_02
Patent number
US08367829B2

Reaction notes

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