Sodium Carbonate → HCID 178435617, compound

HRID 2056110Notes

Reaction equation

HRID 2056110 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][CH:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([NH:39][C:40]3[O:41][C:42]4[CH:48]=[CH:47][C:46]([CH2:49][CH3:50])=[CH:45][C:43]=4[N:44]=3)=[CH:35][CH:34]=2)O1.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>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:38]=[CH:37][C:36]([NH:39][C:40]4[O:41][C:42]5[CH:48]=[CH:47][C:46]([CH2:49][CH3:50])=[CH:45][C:43]=5[N:44]=4)=[CH:35][CH:34]=3)[C:10]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 208170473-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 22346958N2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-ethyl-1,3-benzoxazol-2-amine

Product 1

HCID 178435617HCID 178435617, compoundYield 85.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A mixture of 3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.06 g, 0.00014 mol), N2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-5-ethyl-1,3-benzoxazol-2-amine (0.062 g, 0.00017 mol), tetrakis(triphenylphosphine)palladium (0.011 g, 0.00001 mol) and sodium carbonate (0.037, 0.00035 mol) in ethylene glycol dimethyl ether (3 mL) and water (1 mL) was heated at 80° C. for 16 hours. The mixture was allowed to cool to ambient temperature, and the solvent was removed under the reduced pressure. The residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure, and the residue was purified by flash column chromatography on silica using 2% aqueous ammonium hydroxide solution/5%-25% methanol/dichloromethane as a mobile phase. The solvent was removed under reduced pressure to give cis-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-5-ethyl-1,3-benzoxazol-2-amine (0.065 g, 0.00012 mol). 1H NMR (DMSO-d6, 400 MHz) δ 11.25 (s, 1H), 8.65 (s, 1H), 8.37 (d, 2H), 8.09 (d, 2H), 7.84 (d, 1H), 7.76 (s, 1H), 7.42 (d, 1H), 5.22 (br, 1H), 3.13 (q, 2H), 2.52 (br, 7H), 2.69 (br, 4H), 2.64 (s, 3H), 2.49 (br, 21), 2.11 (br, 2H), 2.01 (br, 2H), 1.63 (t, 3H). RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-95% acetonitrile—0.1M ammonium acetate over 10 min, 1 mL/min) Rt 10.3 min. MS: MH+ 552

Workup

  1. temperatureto cool to ambient temperature
  2. customthe solvent was removed under the reduced pressure
  3. customThe residue was partitioned between water and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×25 mL)
  5. washThe combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvents were evaporated under the reduced pressure
  8. customthe residue was purified by flash column chromatography on silica using 2% aqueous ammonium hydroxide solution/5%-25% methanol/dichloromethane as a mobile phase
  9. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-92bde4091c88425da278fc07c4a90e07
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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