Sodium Bicarbonate → HCID 178480961, compound

HRID 432350Notes

Reaction equation

HRID 432350 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H: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:47]=[CH:46][C:36]([O:37][C:38]3[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=3[CH:40]=[O:41])=[CH:35][CH:34]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>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.CCOCC.COCCOC>[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:34]3[CH:35]=[C:36]([CH:46]=[CH:47][CH:33]=3)[O:37][C:38]3[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=3[CH:40]=[O:41])[C:10]=12

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 2735133Sodium Carbonate MonohydrateHCID 22347138HCID 22347138, compoundHCID 178481014HCID 178481014, compound

Product 1

HCID 178480961HCID 178480961, compoundYield 73.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.970 g, 2.20 mmol, 1 equiv), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]benzaldehyde (0.842 g, 2.60 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.186 g, 0.180 mmol, 0.08 equiv), DME (9 mL), and sodium carbonate monohydrate (0.655 g, 5.30 mmol, 2.4 equiv) in water (7 mL) was heated at 85° C. for 7 h then allowed to cool to ambient temperature. Saturated aqueous sodium bicarbonate solution (50 mL) was added, and the solution was extracted with EtOAc (25 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford a light brown solid. Trituration from Et2O (35 mL) afforded cis-2-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzaldehyde as an off-white solid (0.830 g, 1.62 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 10.42 (1H, s), 8.24 (1H, s), 7.89 (1H, d, J=7.7 Hz), 7.69-7.71 (3H, m), 7.30-7.36 (1H, m), 7.29 (2H, d, J=6.3 Hz), 7.16 (1H, d, J=8.2 Hz), 4.79-4.81 (1H, m), 2.18-2.55 (11H, m), 2.17 (3H, s), 2.05-2.09 (2H, m), 1.56-1.71 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 12.56 min. MS: MH+ 512.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionthe solution was extracted with EtOAc (25 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a light brown solid

Sources & evidence

ORD record
ord-013ff66e109248febedddb468400d135
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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