1-Phenylethanol → 5-chloro-N-(1-methyl-1H-pyrazol-4-yl)-4-(1-phenylethoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 577731Notes

Reaction equation

HRID 577731 reaction equation
Cl[C:2]1[N:3]=[C:4](Cl)[C:5]2[C:10]([Cl:11])=[CH:9][NH:8][C:6]=2[N:7]=1.[C:13]1([CH:19]([OH:21])[CH3:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:22][N:23]1[CH:27]=[C:26]([NH2:28])[CH:25]=[N:24]1>O1CCOCC1.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[Cl:11][C:10]1[C:5]2[C:4]([O:21][CH:19]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH3:20])=[N:3][C:2]([NH:28][C:26]3[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=3)=[N:7][C:6]=2[NH:8][CH:9]=1

Participants

6

Reactant 3

HCID 74091-PhenylethanolHCID 47709901-methyl-1H-pyrazol-4-amineHCID 529877462,4,5-Trichloro-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 866796665-chloro-N-(1-methyl-1H-pyrazol-4-yl)-4-(1-phenylethoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-amineYield 35.6%

Reagents, catalysts & solvents 2

HCID 25112666BrettPhos PalladacycleCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2,4,5-trichloro-7H-pyrrolo[2,3-d]pyrimidine (3.00 g, 13.4 mmol) in 1,4-dioxane (45 mL) was added potassium t-pentoxide (31.2 mL, 1.7 M in toluene) followed by 1-phenylethanol (1.62 mL, 13.4 mmol). The reaction solution was stirred at ambient temperature for 0.5 hr. To the same reaction vessel, 1-methyl-1H-pyrazol-4-amine (1.96 g, 20.2 mmol) and BrettPhos Palladacycle (214 mg, 0.020 mmol) were added and nitrogen gas was bubbled through the reaction mixture for 5 min. The reaction mixture was then sealed and heated to 80° C. for 2 hrs. A black precipitate was filtered off and washed with EtOAc. The combined filtrates were combined and diluted with water (75 mL), extracted EtOAc (2×75 mL), washed with brine, dried over sodium sulfate, filtered and concentrated under in vacuo. The crude residue was purified by flash chromatography (eluting with a gradient of 30%-100% EtOAc in heptanes) to give the title compound (1.76 g, 34%) as a green foam. m/z (APCI+) for C18H17ClN6O 369.1/370.2 (M+H)+.

Workup

  1. customnitrogen gas was bubbled through the reaction mixture for 5 min
  2. customThe reaction mixture was then sealed
  3. temperatureheated to 80° C. for 2 hrs
  4. filtrationA black precipitate was filtered off
  5. washwashed with EtOAc
  6. additiondiluted with water (75 mL)
  7. extractionextracted EtOAc (2×75 mL)
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under in vacuo
  12. customThe crude residue was purified by flash chromatography (
  13. washeluting with a gradient of 30%-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-6dc8ad1945664e8ba3dd78676d385e1e
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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