Cyclohexanecarboxylic acid → HCID 68308532, compound

HRID 1021251Notes

Reaction equation

HRID 1021251 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:29])=[C:12]([C:16]2[CH:17]=[N:18][C:19]([O:22][CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)=[N:20][CH:21]=2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[CH:30]1([C:36](O)=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.ClCCCl>[CH:30]1([C:36]([N:26]2[CH2:27][CH2:28][CH:23]([O:22][C:19]3[N:18]=[CH:17][C:16]([C:12]4[CH:13]=[CH:14][CH:15]=[C:10]([CH2:9][OH:8])[C:11]=4[F:29])=[CH:21][N:20]=3)[CH2:24][CH2:25]2)=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

8

Reactant 5

HCID 7413Cyclohexanecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86686218HCID 86686218, compound

Product 1

HCID 68308532HCID 68308532, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-(piperidin-4-yloxy)pyrimidine (150 mg) and cyclohexane carboxylic acid (82 mg) were mixed with DCE (3.6 ml), and WSC hydrochloride (125 mg) and HOBt (85 mg) were added thereto, followed by stirring at room temperature for 3 hours. A saturated aqueous sodium hydrogen carbonate solution and CHCl3 were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was mixed with THF (3.6 ml), and a 1 M TBAF/THF solution (0.85 ml) was added thereto, followed by stirring at room temperature for 1 hour. EtOAc and an aqueous ammonium chloride solution were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain cyclohexyl [4-({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)piperidin-1-yl]methanone (148 mg).

Workup

  1. additionwere added
  2. dry with materialthe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionThe obtained residue was mixed with THF (3.6 ml)
  5. additiona 1 M TBAF/THF solution (0.85 ml) was added
  6. stirringby stirring at room temperature for 1 hour
  7. additionEtOAc and an aqueous ammonium chloride solution were added to the reaction mixture
  8. dry with materialthe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-4bb7d787483140babe0ac90b68a3f1f1
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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