Dichloromethane → 3-(1,1-dimethylethyl)-6-fluoro-1-methyl-9-(methyloxy)-5-{3-methyl-4-[(phenylmethyl)oxy]phenyl}-8-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinoline

HRID 253288Notes

Reaction equation

HRID 253288 reaction equation
[CH3:1][C:2]([N:5]1[C:9]2[N:10]=[C:11]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[C:38]([CH3:50])[CH:37]=3)[C:12]3[C:13]([F:35])=[CH:14][C:15]([O:20][CH2:21][CH:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]4)=[C:16]([O:18][CH3:19])[C:17]=3[C:8]=2[C:7]([CH3:51])=[N:6]1)([CH3:4])[CH3:3].C(Cl)Cl.C(O)(C(F)(F)F)=O.[OH-].[K+]>C(Cl)(Cl)Cl.O>[CH3:4][C:2]([N:5]1[C:9]2[N:10]=[C:11]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[C:38]([CH3:50])[CH:37]=3)[C:12]3[C:13]([F:35])=[CH:14][C:15]([O:20][CH2:21][CH:22]4[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]4)=[C:16]([O:18][CH3:19])[C:17]=3[C:8]=2[C:7]([CH3:51])=[N:6]1)([CH3:1])[CH3:3]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 668913001,1-dimethylethyl 4-{[(3-(1,1-dimethylethyl)-6-fluoro-1-methyl-9-(methyloxy)-5-{3-methyl-4-[(phenylmethyl)oxy]phenyl}-3H-pyrazolo[3,4-c]isoquinolin-8-yl)oxy]methyl}piperidine-1-carboxylate

Product 1

HCID 668916363-(1,1-dimethylethyl)-6-fluoro-1-methyl-9-(methyloxy)-5-{3-methyl-4-[(phenylmethyl)oxy]phenyl}-8-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinolineYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To 1,1-dimethylethyl 4-{[(3-(1,1-dimethylethyl)-6-fluoro-1-methyl-9-(methyloxy)-5-{3-methyl-4-[(phenylmethyl)oxy]phenyl}-3H-pyrazolo[3,4-c]isoquinolin-8-yl)oxy]methyl}piperidine-1-carboxylate (178 mg, 0.26 mmol) was added CH2Cl2 (3 mL). The solution was cooled with an ice bath and TFA (0.5 mL) was added slowly. After 1 h, the reaction mixture was diluted with CHCl3 and water was added. The mixture was then basified with 1 M KOH (aq) and partitioned. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to provide 3-(1,1-dimethylethyl)-6-fluoro-1-methyl-9-(methyloxy)-5-{3-methyl-4-[(phenylmethyl)oxy]phenyl}-8-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinoline (159 mg, 0.26 mmol, 100% yield) as a yellow sticky solid. 1H NMR (400 MHz, CDCl3): δ 7.51-7.33 (m, 7H), 6.98 (d, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.03 (d, 2H), 3.89 (s, 3H), 3.55 (d, 2H), 3.04-2.95 (m, 2H), 2.88 (s, 3H), 2.37 (s, 3H), 2.26 (m, 1H), 2.16 (d, 2H), 1.85 (s, 9H), 1.88-1.80 (m, 2H); MS (EI) for C36H41FN4O3: 597 (MH+).

Workup

  1. temperatureThe solution was cooled with an ice bath
  2. additionwas added
  3. custompartitioned
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3d8b4b04df734fcea9fe5b1ece7e3540
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

Loading…