5-Bromo-2-fluoropyrimidine → HCID 178521599, compound

HRID 2200767Notes

Reaction equation

HRID 2200767 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](F)=[N:6][CH:7]=1.[NH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([OH:16])[CH2:12][CH2:11]1>CC(O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:9][C@H:10]2[CH2:15][CH2:14][C@H:13]([OH:16])[CH2:12][CH2:11]2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 6006905-Bromo-2-fluoropyrimidineHCID 178511715HCID 178511715, compound

Product 1

HCID 178521599HCID 178521599, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

As shown in step 6-i of Scheme 6, to a mixture of 5-bromo-2-fluoro-pyrimidine (1 g, 5.651 mmol) in iPrOH (10 mL) was added TEA (1.143 g, 1.574 mL, 11.30 mmol) and trans-4-aminocyclohexan-1-ol (650.8 mg, 5.651 mmol). The mixture was microwaved for 20 min at 150° C., concentrated under reduced pressure, diluted with EtOAc, washed with water, and dried over Na2SO4. After removal of the volatiles under reduced pressure, the residue was purified by medium pressure silica gel chromatography (0-80% EtOAc/hexanes gradient) to provide (trans)-4-((5-bromopyrimidin-2-yl)amino)cyclohexanol (compound 1013, 1.2 g): 1H-NMR (300 MHz, CDCl3) δ 8.28 (s, 2H), 5.03 (d, J=8.1 Hz, 1H), 3.91-3.49 (m, 2H), 2.31-1.90 (m, 4H), 1.56-1.19 (m, 4H).

Workup

  1. customThe mixture was microwaved for 20 min at 150° C.
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with EtOAc
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the volatiles under reduced pressure
  7. customthe residue was purified by medium pressure silica gel chromatography (0-80% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-b256a18a32e7471593c23dd522e01ebe
Source dataset
uspto-grants-2016_06
Patent number
US09359380B2

Reaction notes

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