Hydrochloric Acid → 3-(1-(4-amino-3-(5-hydroxy-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one

HRID 634511Notes

Reaction equation

HRID 634511 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:30])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.C([O:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[N:43][C:44]=1[C:45]([F:48])([F:47])[F:46])C1C=CC=CC=1.Cl.[H][H]>CC(O)C.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16](=[O:30])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH3:13])[N:9]=[C:10]([C:41]3[CH:42]=[N:43][C:44]([C:45]([F:47])([F:48])[F:46])=[C:39]([OH:38])[CH:40]=3)[C:3]=12

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1181310533-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-oneHCID 123469151(5-(Benzyloxy)-6-(trifluoromethyl)pyridin-3-yl)boronic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 1181314773-(1-(4-amino-3-(5-hydroxy-6-(trifluoromethyl)pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-oneYield 51.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent

Procedure

The title compound was made in a similar way as that of example 68, using 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate D2a, 100 mg, 0.196 mmol) and (5-(benzyloxy)-6-(trifluoromethyl)pyridin-3-yl)boronic acid (Intermediate G25, 87 mg, 0.295 mmol). The resulting crude material was reacted in 2-Propanol (10 ml) with 1 N aqueous HCl (1 ml), palladium on carbon 5% wet (0.071 mmol) and hydrogen (1 atm). Then, catalyst was filtered off over celite pad and solvent was removed. Target product was purified by purified by C18 flash chromatography (Snap 30 g chromatography ((H2O/ACN)) 95:5+0.1% HCOOH}:{(ACN/H2O) 95:5+HCOOH 0.1%} from 100:0 to 0:100 affording the title compound (20 mg, 0.037 mmol, 51.8% yield) as a white solid.

Workup

  1. filtrationThen, catalyst was filtered off over celite pad and solvent
  2. customwas removed
  3. customTarget product was purified
  4. customby purified by C18 flash chromatography (Snap 30 g chromatography ((H2O/ACN)) 95:5+0.1% HCOOH

Sources & evidence

ORD record
ord-ddb9066373c94f2ebe2f85a75ef7718a
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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