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

HRID 409052Notes

Reaction equation

HRID 409052 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.OC[C@H]1CCCN1C(OC(C)(C)C)=O.[F:39][C:40]1[CH:41]=[C:42]([CH:59]=[CH:60][CH:61]=1)[O:43][C:44]1[CH:49]=[CH:48][C:47](B2OC(C)(C)C(C)(C)O2)=[CH:46][CH:45]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC>[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:47]3[CH:46]=[CH:45][C:44]([O:43][C:42]4[CH:59]=[CH:60][CH:61]=[C:40]([F:39])[CH:41]=4)=[CH:49][CH:48]=3)[C:3]=12

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 710152102-(4-(3-Fluorophenoxy)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 86714462tert-butyl (2R)-2-([4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °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), prepared as described in Example 1 except in the Mitsunobu reaction using (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate instead of (S)-tert-butyl 3-hydroxypiperidine-1-carboxylate, 2-[4-(3-fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (254 mg, 0.81 mmol, 1.20 equiv), tetrakis(triphenylphosphane)palladium (47 mg, 0.04 mmol, 0.06 equiv), ethylene glycol dimethyl ether (50 mL), sodium carbonate (180 mg, 1.70 mmol, 2.50 equiv), and water (10 mL). The resulting solution was stirred for 12 h at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum and extracted with dichloromethane. The organic layers were combined, dried and concentrated under vacuum. The residue was loaded on a silica gel column and eluted with dichloromethane/methanol (50/1) to give 0.27 g (79%) of tert-butyl (2R)-2-([4-amino-3-[4-(3-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate as a brown solid.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. customprepared
  4. customas described in Example 1 except in the Mitsunobu reaction
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. extractionextracted with dichloromethane
  7. customdried
  8. concentrationconcentrated under vacuum
  9. washeluted with dichloromethane/methanol (50/1)

Sources & evidence

ORD record
ord-d1ba5f9225fd4f1d834ee79711105b27
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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