Sodium Carbonate → HCID 22346925, compound

HRID 898027Notes

Reaction equation

HRID 898027 reaction equation
Cl.I[C:3]1[C:11]2[C:6](=[N:7][CH:8]=[N:9][C:10]=2[NH2:12])[N:5]([CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[N:4]=1.[CH3:18][O:19][C:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]=1[NH:35][C:36]([C:38]1[N:39]([CH3:47])[C:40]2[C:45]([CH:46]=1)=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37].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>[NH2:12][C:10]1[N:9]=[CH:8][N:7]=[C:6]2[N:5]([CH:13]3[CH2:17][CH2:16][NH:15][CH2:14]3)[N:4]=[C:3]([C:24]3[CH:23]=[CH:22][C:21]([NH:35][C:36]([C:38]4[N:39]([CH3:47])[C:40]5[C:45]([CH:46]=4)=[CH:44][CH:43]=[CH:42][CH:41]=5)=[O:37])=[C:20]([O:19][CH3:18])[CH:25]=3)[C:11]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideHCID 223473313-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

Product 1

HCID 22346925HCID 22346925, compoundYield 77.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A suspension of 3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride (2.186 g, 5.96 mmol) in ethylene glycol dimethyl ether (50 mL) was treated with N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (2.66 g, 6.56 mmol), tetrakis(triphenylphosphine)palladium (0.413 g, 0.358 mmol), and a solution of sodium carbonate (2.65 g, 25.03 mmol) in water (25 mL). The reaction mixture was stirred for 24 h at 80° C. The organic solvent was removed under reduced pressure. Dichloromethane (100 mL) and 1N sodium hydroxide (50 mL) were added. The product precipitated out of the aqueous layer. The aqueous layer was evaporated under reduced pressure. The resulting solid was washed with copious amounts of dichloromethane and ethyl acetate. The organic solvent was removed under reduced pressure to give 2.218 g (77%) of pure N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.443 (s, 1H), 8.256 (s, 1H), 8.1168-8.0965 (d, 1H, J=8.12 Hz), 7.7181-7.6983 (d, 1H, J=7.92 Hz), 7.598-7.5778 (d, 1H, J=8.08 Hz), 7.349-7.291 (m, 4H), 7.171-7.132 (m, 1H), 5.332-5.313 (m, 1H), 4.041 (s, 3H), 3.96 (s, 3H), 3.224-3.058 (m, 3H), 2.926-2.910 (m, 1H), 2.213-2.158 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.09 min (100%), MH+ 483.3.

Workup

  1. customThe organic solvent was removed under reduced pressure
  2. additionDichloromethane (100 mL) and 1N sodium hydroxide (50 mL) were added
  3. customThe product precipitated out of the aqueous layer
  4. customThe aqueous layer was evaporated under reduced pressure
  5. washThe resulting solid was washed with copious amounts of dichloromethane and ethyl acetate
  6. customThe organic solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-0217cc4b24fa4187bbb7862684696bf6
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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