Diisopropylethylamine → (1R,2S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexane-1,2-diol

HRID 526969Notes

Reaction equation

HRID 526969 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([OH:8])[C@H:3]1[OH:9].[Cl:10][C:11]1[N:16]=[C:15](Cl)[C:14]([F:18])=[CH:13][N:12]=1.CCN(C(C)C)C(C)C>C(#N)C.C(O)(C)C>[Cl:10][C:11]1[N:16]=[C:15]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][C@@H:4]([OH:8])[C@H:3]2[OH:9])[C:14]([F:18])=[CH:13][N:12]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 58369646(1R,2S,3S)-3-aminocyclohexane-1,2-diol

Product 1

HCID 86667420(1R,2S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexane-1,2-diol

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

The starting racemic diol, 31a, (1R,2S,3S)-3-aminocyclohexane-1,2-diol, was prepared following the procedure described in: Org. Bio. Chem. (2008) 6, 3751 and 3762, Davies, et. al. To a solution of racemic diol 31a (0.66 g, 5.00 mmol) in acetonitrile (5 mL) and isopropanol (5 mL) was added 2,4-dichloro-5-fluoro-pyrimidine (0.84 g, 5.03 mmol) and iPr2NEt (3.25 g, 4.38 mL, 25.20 mmol). The reaction mixture was sealed and heated to 100° C. for 90 minutes and then concentrated to dryness. The crude was purified via silica gel chromatography (40%-100% EtOAc/Hex) to afford a racemate, which was further purified via chiral HPLC separation to give compound 31b (0.26 g) as a white solid.

Workup

  1. customThe reaction mixture was sealed
  2. concentrationconcentrated to dryness
  3. customThe crude was purified via silica gel chromatography (40%-100% EtOAc/Hex)
  4. customto afford a racemate, which
  5. customwas further purified via chiral HPLC separation

Sources & evidence

ORD record
ord-2a06026f32034928bdde4ceab33f92b2
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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