Hydrochloric Acid → HCID 67996047, compound

HRID 1907802Notes

Reaction equation

HRID 1907802 reaction equation
[N:1]1([CH2:5][C:6]2[N:10]([CH3:11])[N:9]=[C:8]([NH2:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1.Br[C:14]1[C:15](=[O:22])[N:16](C)[N:17]=[C:18]([Cl:20])[CH:19]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].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.Cl>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].O.C1COCC1.O1CCOCC1>[N:1]1([CH2:5][C:6]2[N:10]([CH3:11])[N:9]=[C:8]([NH:12][C:14]3[C:15](=[O:22])[NH:16][N:17]=[C:18]([Cl:20])[CH:19]=3)[CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2733832Lithium HexamethyldisilazideHCID 585400285-(Azetidin-1-ylmethyl)-1-methyl-1H-pyrazol-3-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 67996047HCID 67996047, compoundYield 66.7%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (20 mL), 22 (500 mg, 3.00 mmol), 25 (630 mg, 3.01 mmol) and 1 M THF solution of lithium hexamethyldisilazide (15 mL, 5.00 mmol). After bubbling nitrogen through the resulting solution for 30 min, Xantphos (148 mg, 0.255 mmol) and tris(dibenzylidene acetone)dipalladium(0) (138 mg, 0.150 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time, the reaction was cooled to room temperature, and water (20 mL) was added. The pH was adjusted to 7 with 1 N hydrochloric acid. The resulting precipitate was collected by vacuum filtration, washed with water (2×25 mL), absorbed on silica gel and purified by flash chromatography to afford an 66% yield (590 mg) of 26 as a light brown solid: mp 140-141° C. 1H NMR (500 MHz, CDCl3) δ 10.63 (s, 1H), 7.78 (s, 1H), 7.46 (s, 1H), 5.84 (s, 1H), 3.81 (s, 3H), 3.52 (s, 2H), 3.23 (t, 4H, J=7.0 Hz), 2.09 (m, 2H); MS (APCI+) m/z 295.8 (M+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser and nitrogen inlet
  3. customAfter bubbling nitrogen through the resulting solution for 30 min
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 3 h
  6. filtrationThe resulting precipitate was collected by vacuum filtration
  7. washwashed with water (2×25 mL)
  8. customabsorbed on silica gel
  9. custompurified by flash chromatography

Sources & evidence

ORD record
ord-107f7756db334363b6488bcf9cfe4660
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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