Sodium Carbonate → tert-butyl (2R)-2-([4-amino-3-[4-(2,3-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)-pyrrolidine-1-carboxylate

HRID 1529886Notes

Reaction equation

HRID 1529886 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[N:9]=[C:10](I)[C:3]=12.[F:25][C:26]1[C:47]([F:48])=[CH:46][CH:45]=[CH:44][C:27]=1[O:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[N:9]=[C:10]([C:32]3[CH:31]=[CH:30][C:29]([O:28][C:27]4[CH:44]=[CH:45][CH:46]=[C:47]([F:48])[C:26]=4[F:25])=[CH:34][CH:33]=3)[C:3]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 710151342-[4-(2,3-Difluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86714463tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate

Product 1

HCID 86714472tert-butyl (2R)-2-([4-amino-3-[4-(2,3-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)-pyrrolidine-1-carboxylateYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 100 mL, 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate (300 mg, 0.68 mmol, 1.00 equiv), a solution of 2-[4-(2,3-difluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (290 mg, 0.87 mmol, 1.10 equiv) in dioxane (9 mL), tetrakis(triphenylphosphane)-palladium (40 mg, 0.03 mmol, 0.05 equiv), and a solution of sodium carbonate (179 mg, 1.67 mmol, 2.50 equiv) in water (3 mL). The resulting solution was stirred for 12 h at 100° C. in an oil bath. The resulting mixture was concentrated under vacuum, and the solution was diluted with ethyl acetate. The resulting mixture was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (20/1) to give 250 mg (71%) of tert-butyl (2R)-2-([4-amino-3-[4-(2,3-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate as a white solid.

Workup

  1. customInto a 100 mL, 3-necked round-bottom flask purged
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionthe solution was diluted with ethyl acetate
  5. washThe resulting mixture was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. washeluted with dichloromethane/methanol (20/1)

Sources & evidence

ORD record
ord-d34c1e68b0cb4d90844d680a18b0b84e
Source dataset
uspto-grants-2015_07
Patent number
US09090621B2

Reaction notes

Loading…