Morpholine → 4-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholine

HRID 1661979Notes

Reaction equation

HRID 1661979 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][C:3]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[F:27].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.[OH-].[K+].[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>C(O)(C)(C)C.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].CCOC(C)=O>[F:27][C:19]1[CH:20]=[C:21]([N+:24]([O-:26])=[O:25])[CH:22]=[CH:23][C:18]=1[O:17][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[N:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1)[N:8]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:7]=[CH:6]2

Participants

9

Reactant 4

HCID 8083MorpholineHCID 14797Potassium HydroxideHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 667669036-Bromo-5-(2-fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

Product 1

HCID 667671464-(5-(2-Fluoro-4-nitrophenoxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-6-yl)morpholineYield 56.5%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-bromo-5-(2-fluoro-4-nitro-phenoxy)-1-(tetrahydropyran-2-yl)-1 H-indazole (8.0 g, 18 mmol) in tert-butanol (150 mL) and H2O (3.2 mL) is added Pd2(dba)3 (320 mg, 0.35 mmol), 2-di-tert-butylphosphino-2′-methylbiphenyl (480 mg, 1.54 mmol), KOH (3.2 g, 57 mmol) and morpholine (3.2 g, 36.7 mmol) under N2. After the mixture is stirred at 70° C. for 2 hours under a N2 atmosphere, it is filtered and the filtrate is concentrated. The residue is partitioned with EtOAc (100 mL) and saturated aqueous NH4Cl (30 mL). The organic layer is separated, dried over MgSO4, and concentrated. The residue is purified by silica gel column chromatography eluting with PE:EtOAc (3:1) to give the product (4.5 g, 56.5% yield). MS (m/z): 443.1 (M+H).

Workup

  1. filtrationit is filtered
  2. concentrationthe filtrate is concentrated
  3. customThe residue is partitioned with EtOAc (100 mL) and saturated aqueous NH4Cl (30 mL)
  4. customThe organic layer is separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography
  8. washeluting with PE

Sources & evidence

ORD record
ord-1cb3a17da64e401d94cf357f5777e4c3
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

Loading…