Sodium Carbonate → HCID 22347369, compound

HRID 897928Notes

Reaction equation

HRID 897928 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[CH3:25][O:26][C:27]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[CH:30][C:28]=1[NH2:29].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[N:9]=[C:10]([C:32]3[CH:31]=[CH:30][C:28]([NH2:29])=[C:27]([O:26][CH3:25])[CH:33]=3)[C:3]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 22346822tert-Butyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate

Product 1

HCID 22347369HCID 22347369, compoundYield 91.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of tert-butyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (0.50 g, 11.26 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.10 g, 12.39 mmol), sodium carbonate (2.90 g, 27.0 mmol) and tetrakis(triphenylphosphine)palladium (0.78 g, 0.67 mmol) in ethylene glycol dimethyl ether (90 mL) and water (45 mL) was heated at 85° C. for 18 hours. The mixture was cooled and evaporated under reduced pressure then partitioned between water (50 mL) and dichloromethane (50 mL). The aqueous layer was extracted further with dichloromethane (2×50 mL) then the combined organic solutions were dried over magnesium sulfate and then filtered. The filtrate was concentrated and purified by flash chromatography on silica gel using dichloromethane/methanol (96:4) as an eluent to provide the title compound (4.51 g, 91%) as a tan solid: 1H NMR (DMSO-d6, 400 MHz) δ 8.20 (s, 1H), 7.04 (s, 1H), 6.98 (d, 1H), 6.76 (d, 1H), 5.06 (bs, 1H), 4.86 (m, 1H), 4.08 (m, 2H), 3.83 (s, 3H), 2.90 (m, 2H), 2.03 (m, 2H), 1.90 (m, 2H), 1.43 (s, 9H); RP-HPLC (Hypersil HS C18 Hypersil HS C18, 5 μm 100 A, 250×4.6 mm; 25%-100% acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) tr 9.70 min.

Workup

  1. temperatureThe mixture was cooled
  2. customevaporated under reduced pressure
  3. customthen partitioned between water (50 mL) and dichloromethane (50 mL)
  4. extractionThe aqueous layer was extracted further with dichloromethane (2×50 mL)
  5. dry with materialthe combined organic solutions were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-807642fcea6b4450aa9b96a712657568
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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