Dichloromethane → 5-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamide

HRID 1487630Notes

Reaction equation

HRID 1487630 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:27][NH:28][C:29](=[O:45])[C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>O.O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:33]3[CH:34]=[CH:35][C:30]([C:29]([NH:28][CH3:27])=[O:45])=[N:31][CH:32]=3)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44119560N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamideHCID 867264332-Chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867264585-(2-Chloro-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylpicolinamideYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

2-Chloro-5-iodo-4-(tetrahydro-2H-pyran-4-yloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamide (1 equiv), 1′-bis(diphenyl-phosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (0.1 equiv), sodium carbonate (3 equiv) were suspended in a 3:1 mixture of 1,4-dioxane and water (0.09 M) were combined in a sealed reaction vessel. The resulting solution was flushed with nitrogen and stirred at 85° C. for 2 h. After cooling to room temperature the reaction mixture was loaded directly onto a silica-gel column and purified using flash chromatography (0-55% ethyl acetate in hexane). Fractions were combined, concentrated and the residue dried under high vacuum to give the title compound (61% yield) as a brown semi solid. MS (ESI) m/z 519.1 [M+1]+.

Workup

  1. customwere combined in a sealed reaction vessel
  2. customThe resulting solution was flushed with nitrogen
  3. temperatureAfter cooling to room temperature the reaction mixture
  4. custompurified
  5. concentrationconcentrated
  6. customthe residue dried under high vacuum

Sources & evidence

ORD record
ord-96fe63531b3b415985824b2f7e6b0be1
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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