1,2-Diaminocyclohexane, trans- → 2-Chloro-7-(3,5-difluoro-4-morpholin-4-ylmethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1966395Notes

Reaction equation

HRID 1966395 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[CH:9][NH:8][C:6]=2[N:7]=1.Br[C:12]1[CH:24]=[C:23]([F:25])[C:15]([CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[C:14]([F:26])[CH:13]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N>O1CCOCC1.[Cu]I>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[CH:9][N:8]([C:12]3[CH:13]=[C:14]([F:26])[C:15]([CH2:16][N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[C:23]([F:25])[CH:24]=3)[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 57067742-Chloro-7H-pyrrolo[2,3-d]pyrimidineHCID 59392758HCID 59392758, compound

Product 1

HCID 866332712-Chloro-7-(3,5-difluoro-4-morpholin-4-ylmethyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a sealed tube, 2-chloro-7H-pyrrolo[2,3-d]pyrimidine (200 mg, 1.24 mmol), 4-(4-bromo-2,6-difluoro-benzyl)-morpholine (418 mg, 1.36 mmol), CuI (72.1 mg, 0.371 mmol), and K3PO4 (804 mg, 3.71 mmol) are suspended in 1,4-dioxane (8 mL). Then, trans-1,2-diaminocyclohexane (45.0 μL, 0.371 mmol) is added at rt. The reaction vial is flushed with Ar and the mixture is heated to 110° C. for 5 h. After cooling to rt, the reaction mixture is diluted with EtOAc and the organic layer is washed with saturated aqueous Na2CO3 solution (2×). The organic layer is dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography (SiO2, gradient elution, hexane/EtOAc 100:0→30:70) to yield the title compound as a white solid.

Workup

  1. customThe reaction
  2. customvial is flushed with Ar
  3. temperatureAfter cooling to rt
  4. additionthe reaction mixture is diluted with EtOAc
  5. washthe organic layer is washed with saturated aqueous Na2CO3 solution (2×)
  6. dry with materialThe organic layer is dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by column chromatography (SiO2, gradient elution, hexane/EtOAc 100:0→30:70)

Sources & evidence

ORD record
ord-f04bb361344244f7a8b61804cb035ab2
Source dataset
uspto-grants-2013_04
Patent number
US08420657B2

Reaction notes

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