Dichloromethane → 4-(2-Chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

HRID 1487586Notes

Reaction equation

HRID 1487586 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:25][CH2:24][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.[CH3:26][NH:27][C:28]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)=[O:29].C(=O)([O-])[O-].[Na+].[Na+].ClCCl>O1CCOCC1.O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:33]3[CH:34]=[CH:35][C:30]([C:28]([NH:27][CH3:26])=[O:29])=[CH: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

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 867264232-Chloro-4-(cyclopentyloxy)-5-iodo-7-[[2-(trimethylsilyl)ethoxy]methyl]-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867264224-(2-Chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamideYield 62.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

2-Chloro-4-(cyclopentyloxy)-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv) and (4-(methylcarbamoyl)phenyl)boronic acid (1.3 equiv) were combined in 1,4-dioxane (0.3 M). Sodium carbonate (3 equiv), dissolved in water (3.6 M), was added to the reaction mixture, followed by addition of [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (0.1 equiv). Nitrogen gas was bubbled through the reaction mixture for 2 min then reaction was heated at 90° C. for 3 h. The solvent was removed under reduced pressure and the product was purified by silica gel chromatography (Biotage, 0-80% ethyl acetate in hexane over 2.2 L). The fractions containing the desired product were combined and evaporated under reduced pressure to give the title compound (62.5% yield) as an orange solid. MS (ESI) m/z 501.4 [M+1]+.

Workup

  1. additionwas added to the reaction mixture
  2. customNitrogen gas was bubbled through the reaction mixture for 2 min
  3. customreaction
  4. customThe solvent was removed under reduced pressure
  5. customthe product was purified by silica gel chromatography (Biotage, 0-80% ethyl acetate in hexane over 2.2 L)
  6. additionThe fractions containing the desired product
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d13945cf6d604790b01926c2c0416369
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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