Sodium Carbonate → tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate

HRID 2056136Notes

Reaction equation

HRID 2056136 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)[N:3]=1.[CH3:19][O:20][C:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:22]=1[NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:12]3[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]3)[N:3]=[C:2]([C:25]3[CH:24]=[CH:23][C:22]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[C:21]([O:20][CH3:19])[CH:26]=3)[C:10]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 223471833-iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 22347171tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamateYield 73.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine (52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed in ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69 (s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight under nitrogen
  3. customOrganic solvent was removed under reduced pressure
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. washThe combined organic layer was washed with water
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-fe0f079f3ee4410caa68fef365b6552a
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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