Dichloromethane → Methyl 9-(1-isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylate

HRID 886013Notes

Reaction equation

HRID 886013 reaction equation
[CH:1]([N:4]1[C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].I[C:19]1[N:23]2[C:24]3[N:32]=[CH:31][C:30]([C:33]([O:35][CH3:36])=[O:34])=[CH:29][C:25]=3[O:26][CH2:27][CH2:28][C:22]2=[N:21][CH:20]=1.ClCCl.C([O-])(=O)C.[K+].COCCOC>O.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]>[CH:1]([N:4]1[C:8]([C:20]2[N:21]=[C:22]3[CH2:28][CH2:27][O:26][C:25]4[CH:29]=[C:30]([C:33]([O:35][CH3:36])=[O:34])[CH:31]=[N:32][C:24]=4[N:23]3[CH:19]=2)=[CH:7][CH:6]=[N:5]1)([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 80711,2-DimethoxyethaneHCID 517044Potassium AcetateHCID 567767101-(Propan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86652295Methyl 10-iodo-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylate

Product 1

HCID 58204755Methyl 9-(1-isopropyl-1H-pyrazol-5-yl)-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A mixture of 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (117.1 mg, 0.4958 mmol), methyl 10-iodo-6,7-dihydroimidazo[1,2-d]pyrido[3,2-b][1,4]oxazepine-3-carboxylate (92.0 mg, 0.248 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (20.24 mg, 0.02479 mmol) and 1.0 M of Potassium acetate in water (0.49 mL) in 1,2-Dimethoxyethane (5.0 mL, 48 mmol) was degassed. The reaction was microwaved on 200 watts, 140° C. for 40 minutes. The reaction mixture was filtered, washed with DME, mixed with water and extracted with EtOAc. Combined organic extracts were washed with 1% aq NaOH to remove a phenolic byproduct, then 5% aq citric acid, water, brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified on 4 g silica column, eluting with 60-70% of EtOAc in heptane. Yield 21 mg. MS (ESI+): 354.2.

Workup

  1. customwas degassed
  2. customThe reaction was microwaved on 200 watts, 140° C. for 40 minutes
  3. filtrationThe reaction mixture was filtered
  4. washwashed with DME
  5. additionmixed with water
  6. extractionextracted with EtOAc
  7. washCombined organic extracts were washed with 1% aq NaOH
  8. customto remove a phenolic byproduct
  9. dry with material5% aq citric acid, water, brine, dried over Na2SO4
  10. concentrationconcentrated in vacuum
  11. customThe residue was purified on 4 g silica column
  12. washeluting with 60-70% of EtOAc in heptane

Sources & evidence

ORD record
ord-5e3842959cd848ada7359c42af8b0a23
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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