Sodium Carbonate → HCID 86677690, compound

HRID 1499759Notes

Reaction equation

HRID 1499759 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:33][CH2:34][CH3:35])=[C:16]([C:22]4[CH:23]=[CH:24][C:25]([C:28]([N:30]([CH3:32])[CH3:31])=[O:29])=[N:26][CH:27]=4)[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[CH3:36][C:37]1(C)C(C)(C)OB(C=C)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.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:33][CH2:34][CH3:35])=[C:16]([C:22]4[CH:23]=[CH:24][C:25]([C:28]([N:30]([CH3:32])[CH3:31])=[O:29])=[N:26][CH:27]=4)[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[N:9]=[C:10]([CH:36]=[CH2:37])[C:3]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 71510766HCID 71510766, compound2×

Product 1

HCID 86677690HCID 86677690, compoundYield 88.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-{3-[1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-methylphenyl}-N,N-dimethylpyridine-2-carboxamide (130 mg, 0.21 mmol, racemic intermediate from Example 15), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (66 mg, 0.43 mmol), sodium carbonate (136 mg, 1.29 mmol) in N,N-dimethylformamide (1 mL)/water (0.64 mL) under N2 was added tetrakis(triphenylphosphine)palladium(0) (25 mg, 0.021 mmol). The mixture was heated at 100° C. overnight. After cooling to room temperature, the mixture was diluted with water, and extracted with dichloromethane. The organic layers were concentrated and purified on silica gel (eluting with 0 to 100% EtOAc in hexanes followed by 0 to 10% MeOH in dichloromethane) to give the desired product (94 mg, 86%), LCMS calculated for C26H29ClN7O2 (M+H)+: m/z=506.2; Found: 506.2.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with dichloromethane
  3. concentrationThe organic layers were concentrated
  4. custompurified on silica gel (eluting with 0 to 100% EtOAc in hexanes followed by 0 to 10% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-a1d8fad3d51c4897af358a3ac8b7b6d3
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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