Morpholine → HCID 86686707, compound

HRID 75607Notes

Reaction equation

HRID 75607 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23](Br)[CH:22]=2)[N:19]=[C:18]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:17]=1)C(OC(C)(C)C)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.CC(C)([O-])C.[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1COCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:7])[NH:8][C:16]1[N:20]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:22]=2)[N:19]=[C:18]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:17]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23665647Potassium tert-butoxideHCID 86686706Di-tert-butyl(1-(3-bromophenyl)-3-tert-butyl-1H-pyrazol-5-yl]imidodicarbonate

Product 1

HCID 86686707HCID 86686707, compoundYield 40.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of Intermediate 23b (900 mg, 1.80 mmol), morpholine (240 mg, 2.70 mmol), potassium-tert-butoxide (303 mg, 2.70 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl biphenyl (87 mg, 0.18 mmol), and tris(dibenzylideneacetone)dipalladium(0) (81 mg, 0.09 mmol) in THF (9 mL) was irradiated in the microwave at 100° C. for 20 min. The reaction was diluted with water and extracted with EtOAc (×2). The combined organics were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-100% EtOAc in cyclohexane, to give the title compound (290 mg, 40%). LCMS (Method 7): Rt 3.94 min, m/z 401 [MH+].

Workup

  1. customwas irradiated in the microwave at 100° C. for 20 min
  2. extractionextracted with EtOAc (×2)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-b5ab8733ecf54049a5b9c16eca61a0cd
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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