4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one → 4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one

HRID 634515Notes

Reaction equation

HRID 634515 reaction equation
[C:1]([N:4]1[CH2:9][CH:8]=[C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[O:12][C:11]=2[CH:21]([N:23]2[C:27]3=[N:28][CH:29]=[N:30][C:31]([NH2:32])=[C:26]3[C:25]([C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([O:40][Si](C(C)(C)C)(C)C)[CH:34]=3)=[N:24]2)[CH3:22])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]>Cl.CCO>[C:1]([N:4]1[CH2:5][CH:6]=[C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[O:12][C:11]=2[CH:21]([N:23]2[C:27]3=[N:28][CH:29]=[N:30][C:31]([NH2:32])=[C:26]3[C:25]([C:33]3[CH:34]=[C:35]([OH:40])[CH:36]=[C:37]([F:39])[CH:38]=3)=[N:24]2)[CH3:22])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

4

Reactant 1

HCID 1231689484-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one

Product 1

HCID 1181312574-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-oneYield 93%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one single enantiomer (intermediate T.2, first eluted enantiomer under the conditions described above, 0.350 g, 0.535 mmol) was dissolved in a solution of 1M HCl in EtOH (1.7 ml) and the mixture was stirred at RT overnight. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography on silica gel cartridge (DCM to DCM:MeOH=95:5) to afford title compound as a yellow solid (0.270 g, 0.500 mmol, 93%). This compound proved to be the second eluted enantiomer under Chiral HPLC conditions of Method A11: Rt=15.8 min, ee=99.4%.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue was purified by flash chromatography on silica gel cartridge (DCM to DCM:MeOH=95:5)

Sources & evidence

ORD record
ord-7e25fed5ae5a4cff9ed2fc30040d1291
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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