Cesium carbonate → HCID 71008562, compound

HRID 1025604Notes

Reaction equation

HRID 1025604 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:31][OH:32])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]#[N:29])[C:25](I)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=1.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-].[Cs+].[Cs+]>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].O1CCOCC1>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[C:18]([CH2:31][OH:32])=[C:19]([N:23]3[CH:27]=[C:26]([C:28]#[N:29])[C:25]([NH:40][C:37]4[CH:36]=[CH:35][C:34]([Cl:33])=[CH:39][N:38]=4)=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 661742-Amino-5-chloropyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 71008281HCID 71008281, compound

Product 1

HCID 71008562HCID 71008562, compoundYield 52.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

A small round bottom flask was charged with 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-iodo-1H-pyrazole-4-carbonitrile (212 mg, 0.39 mmol), 5-chloropyridin-2-amine (65 mg, 0.51 mmol), XANTPHOS (56 mg, 0.098 mmol), and cesium carbonate (381 mg, 1.17 mmol). Dry dioxane (5.7 ml) was added and the mixture was thoroughly degassed with argon. Pd2(dba)3 (46 mg, 0.051 mmol) was added and the material was again degassed with argon. The flask was placed in an oil bath heated to 95° C. for 2.5 hours. The flask was cooled to ambient and ethyl acetate (30 ml) and water (30 ml) were added. The contents were shaken in a separatory funnel and the organic phase was collected. The aqueous phase was back extracted with ethyl acetate (2×30 ml), and the organic phase was combined, dried with magnesium sulfate, filtered and stripped. The crude material was purified by preparative thin layer chromatography (2 plates, eluting with 4% methanol in methylene chloride). The product band was collected, providing the desired 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-3-(5-chloro-pyridin-2-ylamino)-1H-pyrazole-4-carbonitrile as a light yellow powder (111 mg). LC/MS calc'd for C28H23ClFN7O2 (m/e) 543.98, obs'd 544 (M+H, ES+).

Workup

  1. customthe mixture was thoroughly degassed with argon
  2. customthe material was again degassed with argon
  3. customThe flask was placed in an oil bath
  4. temperatureThe flask was cooled to ambient and ethyl acetate (30 ml) and water (30 ml)
  5. additionwere added
  6. customthe organic phase was collected
  7. extractionThe aqueous phase was back extracted with ethyl acetate (2×30 ml)
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. customThe crude material was purified by preparative thin layer chromatography (2 plates, eluting with 4% methanol in methylene chloride)
  11. customThe product band was collected

Sources & evidence

ORD record
ord-80dbc560b5a34feb99b2116df292c39e
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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