HCID 123825481, compound → HCID 118131051, compound

HRID 634518Notes

Reaction equation

HRID 634518 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:26]([C:28]3[O:29][C:30](=[O:43])[C:31]4[C:36]([C:37]=3[C:38]3[S:42][CH:41]=[N:40][CH:39]=3)=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:27])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([O:18][Si](C(C)(C)C)(C)C)[CH:12]=3)[C:3]=12>Cl.CCO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:26]([C:28]3[O:29][C:30](=[O:43])[C:31]4[C:36]([C:37]=3[C:38]3[S:42][CH:41]=[N:40][CH:39]=3)=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:27])[N:9]=[C:10]([C:11]3[CH:12]=[C:13]([OH:18])[CH:14]=[C:15]([F:17])[CH:16]=3)[C:3]=12

Participants

4

Reactant 1

HCID 123825481HCID 123825481, compound

Product 1

HCID 118131051HCID 118131051, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolvent

Procedure

3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(thiazol-5-yl)-1H-isochromen-1-one single enantiomer (intermediate R2, first eluted enantiomer under the conditions described above, 0.084 g, 0.13 mmol) was dissolved in a solution of 1M HCl in EtOH (0.416 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 pale blue solid (0.043 g, 0.086 mmol, 66%). This compound proved to be the first eluted enantiomer under Chiral HPLC conditions of Method A7: Rt=16.0 min, ee>99%.

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-da14c3b635b74712a7b674d36f57ecc2
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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