Sodium Carbonate → tert-butyl (3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate

HRID 2207503Notes

Reaction equation

HRID 2207503 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][CH:45]=[C:44]([F:48])[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[C:44]([F:48])=[CH:45][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 669155272-(4-(2,6-Difluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 86714490tert-butyl (3R)-3-[4-amino-3-[4-(2,6-difluorophenoxy)-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylateYield 85%

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-(2,6-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 15 h at 90° C. in an oil bath and then concentrated under vacuum. The residue was diluted with water and extracted with dichloromethane and the organic layers combined. The organics were washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (10/1) to give 500 mg (85%) of tert-butyl (3R)-3-[4-amino-3-[4-(2,6-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. extractionextracted with dichloromethane
  6. washThe 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-fcb1219729a948c18c0f14c664e58491
Source dataset
uspto-grants-2016_06
Patent number
US09376438B2

Reaction notes

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