Water → HCID 136334044, compound

HRID 1499770Notes

Reaction equation

HRID 1499770 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:27][CH2:28][CH3:29])=[C:16]([C:22]([CH3:26])=[C:23]([Cl:25])[CH:24]=3)[C:17]([NH:19][CH2:20][CH3:21])=[O:18])[CH3:13])[N:9]=[C:10](I)[C:3]=12.CC1(C)C(C)(C)OB([C:38]2[CH:39]=[N:40][NH:41][CH:42]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>CN(C)C=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>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[C:15]([O:27][CH2:28][CH3:29])=[C:16]([C:22]([CH3:26])=[C:23]([Cl:25])[CH:24]=3)[C:17]([NH:19][CH2:20][CH3:21])=[O:18])[CH3:13])[N:9]=[C:10]([C:38]3[CH:39]=[N:40][NH:41][CH:42]=3)[C:3]=12

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86677701HCID 86677701, compound

Product 1

HCID 136334044HCID 136334044, compoundYield 11.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-[1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-N-ethyl-6-methylbenzamide (9.0 mg, 0.017 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (6.6 mg, 0.034 mmol), sodium carbonate (11 mg, 0.10 mmol) in N,N-dimethylformamide (0.1 mL)/water (51 μL) under N2 was added tetrakis(triphenylphosphine)palladium(0) (2.0 mg, 0.0017 mmol). The mixture was heated at 100° C. overnight. After cooling to room temperature, the mixture was filtered and purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (0.9 mg, 10%). The product was isolated as a racemic mixture. LCMS calculated for C22H26ClN8O2 (M+H)+: m/z=469.2; Found: 469.0.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered
  3. custompurified on RP-HPLC (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-a59003377bc94b3692b885d69c0707d7
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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