Sodium Carbonate → HCID 86714495, compound

HRID 1843371Notes

Reaction equation

HRID 1843371 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[F:25][C:26]1[CH:47]=[CH:46][C:45]([F:48])=[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.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10]([C:32]3[CH:31]=[CH:30][C:29]([O:28][C:27]4[CH:44]=[C:45]([F:48])[CH:46]=[CH:47][C:26]=4[F:25])=[CH:34][CH:33]=3)[C:3]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58441419(R)-tert-Butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylateHCID 71014103HCID 71014103, compound

Product 1

HCID 86714495HCID 86714495, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

Into a 250-mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of tert-butyl (3R)-3-[4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate (500 mg, 1.13 mmol, 1.00 equiv) in 1,4-dioxane/H2O (100/30 mL), 2-[4-(2,5-difluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (420 mg, 1.26 mmol, 1.1 equiv), sodium carbonate (240 mg, 2.26 mmol, 2.0 equiv), and Pd(PPh3)4 (65 mg, 0.06 mmol, 0.05 equiv). The resulting solution was stirred for 12 h at 90° C. in an oil bath and then concentrated under vacuum. The residue was diluted with water and the resulting solution was extracted with dichloromethane and the organic layers were combined. The combined organics were washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel and eluted with dichloromethane/methanol (10/1) to give 510 mg (87%) of tert-butyl (3R)-3-[4-amino-3-[4-(2,5-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate as a white solid.

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. concentrationconcentrated under vacuum
  4. additionThe residue was diluted with water
  5. extractionthe resulting solution was extracted with dichloromethane
  6. washThe combined organics were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. washeluted with dichloromethane/methanol (10/1)

Sources & evidence

ORD record
ord-f935d9196c794f38bf94d445fa3a7847
Source dataset
uspto-grants-2015_02
Patent number
US08946241B2

Reaction notes

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