HCID 123825481, compound → HCID 118131051, compound

HRID 634519Notes

Reaction equation

HRID 634519 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 74%

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 R.3, second eluted enantiomer under the conditions described above, 0.089 g, 0.14 mmol) was dissolved in a solution of 1M HCl in EtOH (0.5 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 (0.048 g, 0.096 mmol, 74%). This compound proved to be the second eluted enantiomer under Chiral HPLC conditions of Method A7: Rt=20.1 min, ee=98.4%.

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-0591e6d909e64ab1b877a0ccc01f0152
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

Loading…