Diisopropylethylamine → HCID 86667449, compound

HRID 527069Notes

Reaction equation

HRID 527069 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:3]1.[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([F:21])=[CH:16][N:15]=1.C(N(C(C)C)CC)(C)C>C1COCC1>[Cl:13][C:14]1[N:19]=[C:18]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][C@@H:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:3]2)[C:17]([F:21])=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 12636188(1R,3S)-ethyl 3-aminocyclohexanecarboxylate2×

Product 1

HCID 86667449HCID 86667449, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1R,3S)-ethyl 3-aminocyclohexanecarboxylate, 67b, (5.1 g, 24.1 mmol) and 2,4-dichloro-5-fluoropyrimidine (6.0 g, 36.0 mmol) in THF (60 mL) was added diisopropylethylamine (9.6 mL, 55.4 mmol). The mixture was heated to reflux overnight. The reaction was cooled to room temperature and concentrated in vacuo. The residue was diluted with water and extracted twice with ethyl acetate. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-40% EtOAc/hexanes gradient) to provide 6.7 g of (1R,3S)-ethyl 3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexane-carboxylate as a white solid: LCMS RT=3.1 (M+H) 302.2.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with water
  5. extractionextracted twice with ethyl acetate
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (0-40% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-22218b387cab4f4295a9ee815e282e2f
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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