Sodium Carbonate → HCID 178480975, compound

HRID 897722Notes

Reaction equation

HRID 897722 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13](B4OC(C)(C)C(C)(C)O4)=[CH:12][CH:11]=3)[S:8][C:4]=2[CH:3]=1.I[C:28]1[C:36]2[C:31](=[N:32][CH:33]=[N:34][C:35]=2[NH2:37])[N:30]([C@H:38]2[CH2:43][CH2:42][C@@H:41]([N:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[CH2:40][CH2:39]2)[N:29]=1.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>[NH2:37][C:35]1[N:34]=[CH:33][N:32]=[C:31]2[N:30]([C@H:38]3[CH2:43][CH2:42][C@@H:41]([N:44]4[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]4)[CH2:40][CH2:39]3)[N:29]=[C:28]([C:13]3[CH:12]=[CH:11][C:10]([NH:9][C:7]4[S:8][C:4]5[CH:3]=[C:2]([Cl:1])[CH:26]=[CH:25][C:5]=5[N:6]=4)=[CH:15][CH:14]=3)[C:36]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 22347348HCID 22347348, compoundHCID 178481014HCID 178481014, compound

Product 1

HCID 178480975HCID 178480975, compoundYield 25.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Procedure for Suzuki coupling: A mixture of N-(6-chloro-1,3-benzothiazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.116 g, 0.30 mmol), cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.106 g, 0.24 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.014 g, 0.012 mmol) in ethylene glycol dimethyl ether (3.0 mL), sodium carbonate (0.064 g, 0.60 mmol), and water (1.5 mL) in a sealed Schlenk flask were heated at 90° C. for 24 h. The mixture was cooled, diluted with water (10 mL) and extracted with methanol/dichloromethane (1:19, 3×20 mL). The combined organic fractions were dried (magnesium sulfate), filtered, concentrated and purified by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8μ Hypersil HS C18, 250×21 mm column, Rt 7.8-10.0 min) to afford cis-N2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-6-chloro-1,3-benzothiazol-2-amine as a yellow powder (0.036 g, 0.062 mmol); RP-HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a 5μ Hypersil HS C18, 250×4.6 mm column) Rt 8.42 min;

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with methanol/dichloromethane (1:19, 3×20 mL)
  3. dry with materialThe combined organic fractions were dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

Sources & evidence

ORD record
ord-63fa0fa54b5649d09956792f5fb85c4f
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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