Sodium Bicarbonate → HCID 58072243, compound

HRID 1407354Notes

Reaction equation

HRID 1407354 reaction equation
Br[C:2]1[C:3]([F:28])=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]3[N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:20]=[CH:19][CH:18]=3)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.Cl.[F:30][C:31]1([F:38])[C:35]([F:37])([F:36])[CH2:34][NH:33][CH2:32]1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])(O)=O.[Na+]>O1CCOCC1.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]>[F:28][C:3]1[C:2]([N:33]2[CH2:34][C:35]([F:37])([F:36])[C:31]([F:38])([F:30])[CH2:32]2)=[CH:7][CH:6]=[CH:5][C:4]=1[N:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]2[N:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:20]=[CH:19][CH:18]=2)=[N:9]1

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 226459203,3,4,4-Tetrafluoropyrrolidine HydrochlorideHCID 23676156Sodium t-butoxideHCID 58072344HCID 58072344, compound

Product 1

HCID 58072243HCID 58072243, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 1-(3-bromo-2-fluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (221 mg, 0.500 mmol), 3,3,4,4-tetrafluoropyrrolidine hydrochloride (108 mg, 0.600 mmol), sodium tert-butoxide (125 mg, 1.300 mmol), Xantphos (23 mg, 0.040 mmol), and tris(dibenzylideneacetone)dipalladium(0) (9 mg, 0.010 mmol) in 1,4-dioxane (2.5 mL) was stirred at 90° C. under Ar atmosphere. The reaction mixture was poured into 5% NaHCO3 aqueous solution (20 mL) and extracted with AcOEt (20 mL×3). The combined organic phase was washed with brine (40 mL), dried with MgSO4, and evaporated. The residue was purified by silica gel column chromatography (AcOEt/hexane=60%-100%) to give the title compound (95.4 mg, 38% yield) as an amorphous solid: 1H NMR (300 MHz, CDCl3): δ ppm 3.84-3.96 (7H, m), 6.11 (1H, t, J=7.5 Hz), 6.60 (1H, td, J=8.3, 1.5 Hz), 6.90-6.98 (1H, m), 7.25 (1H, d, J=1.9 Hz), 7.33-7.41 (5H, m), 7.70 (1H, d, J=2.6 Hz), 7.78 (1H, d, J=1.9 Hz). LC-MS (ESI) m/z 504 [M+H]+.

Workup

  1. extractionextracted with AcOEt (20 mL×3)
  2. washThe combined organic phase was washed with brine (40 mL)
  3. dry with materialdried with MgSO4
  4. customevaporated
  5. customThe residue was purified by silica gel column chromatography (AcOEt/hexane=60%-100%)

Sources & evidence

ORD record
ord-10c928e69d644f8cb598abe545f06db6
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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