3,6-Dihydro-2H-pyran-4-boronic acid pinacol ester → HCID 90408541, compound

HRID 594077Notes

Reaction equation

HRID 594077 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=2[CH3:15])[NH2:11])[CH:5]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:3]=1.[O:22]1[CH2:27][CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH2:24][CH2:23]1>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[O:22]1[CH2:23][CH:24]=[C:25]([C:2]2[CH:7]=[C:6]([C:8]3[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=3[CH3:15])[NH2:11])[CH:5]=[C:4]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[N:3]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 2

HCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 90408835HCID 90408835, compound

Product 1

HCID 90408541HCID 90408541, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a solution of 3-(2-chloro-6-morpholinopyridin-4-yl)-4-methylaniline (1.0 equiv.) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.2 equiv.) in DME and 2M sodium carbonate (3:1, 0.1 M) was added PdCl2(dppf)-DCM adduct (0.1 equiv.). The solution was heated to 100 C for 5 hours. Upon cooling to room temperature, the solution was partitioned between water and ethyl acetate, the organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified via silica gel column chromatography eluting with 0-50% ethyl acetate and heptanes). The pure fractions were concentrated to yield 3-(2-(3,6-dihydro-2H-pyran-4-yl)-6-morpholinopyridin-4-yl)-4-methylaniline in 69% yield. LCMS (m/z) (M+H)=352.3, Rt=0.50 min.

Workup

  1. temperatureThe solution was heated to 100 C for 5 hours
  2. customthe solution was partitioned between water and ethyl acetate
  3. dry with materialthe organic phase was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via silica gel column chromatography
  7. washeluting with 0-50% ethyl acetate and heptanes)
  8. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-e9637b18600744e392676b13a178f15a
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

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