Dichloromethane → 6-(2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

HRID 529665Notes

Reaction equation

HRID 529665 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([Cl:20])[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.[CH3:21][C:22]1[O:23][C:24]2[CH:30]=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:28]=[CH:27][C:25]=2[N:26]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([Cl:20])[C:5]2[C:10]([C:29]3[CH:28]=[CH:27][C:25]4[N:26]=[C:22]([CH3:21])[O:23][C:24]=4[CH:30]=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 709750612-Methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-benzoxazoleHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 867264196-(2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazoleYield 72%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

To a solution of 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole (1 equiv), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with DCM (0.1 equiv) in a 3:1 mixture of 1,4-dioxane and water (0.2 M) was added sodium carbonate (3 equiv). The reaction was stirred at 85° C. for 15 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then extracted with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (0-50% ethyl acetate in hexane) to give the title compound (72.0% yield) as a brown oil 1H NMR (400 MHz, DMSO-d6) δ ppm −0.06 (s, 9 H) 0.83-0.92 (m, 2 H) 2.64 (s, 3 H) 3.55-3.65 (m, 2 H) 5.65 (s, 2 H) 7.47 (dd, J=8.00, 1.76 Hz, 1 H) 7.72 (d, J=8.20 Hz, 1 H) 7.79-7.83 (m, 1 H) 8.05 (s, 1 H); MS (ESI) m/z 449.5 [M+1]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  2. extractionextracted with ethyl acetate
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by silica gel column chromatography (0-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e0f26c7b99bd4b9380c17eed80298891
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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