Diisopropylethylamine → HCID 178429918, compound

HRID 921546Notes

Reaction equation

HRID 921546 reaction equation
[SH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([OH:8])[CH2:4][CH2:3]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(N(CC)C(C)C)(C)C.Br[C:61]1[CH:68]=[C:67]([N:69]2[C:73]3=[N:74][CH:75]=[CH:76][C:77]([C:78]4[CH:79]=[N:80][C:81]5[C:86]([CH:87]=4)=[CH:85][CH:84]=[CH:83][CH:82]=5)=[C:72]3[C:71]([CH3:88])=[CH:70]2)[CH:66]=[CH:65][C:62]=1[C:63]#[N:64]>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].O.C(OCC)(=O)C>[OH:8][C@H:5]1[CH2:6][CH2:7][C@H:2]([S:1][C:65]2[CH:66]=[C:67]([N:69]3[C:73]4=[N:74][CH:75]=[CH:76][C:77]([C:78]5[CH:79]=[N:80][C:81]6[C:86]([CH:87]=5)=[CH:85][CH:84]=[CH:83][CH:82]=6)=[C:72]4[C:71]([CH3:88])=[CH:70]3)[CH:68]=[CH:61][C:62]=2[C:63]#[N:64])[CH2:3][CH2:4]1

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67500186HCID 67500186, compoundHCID 178521616HCID 178521616, compound

Product 1

HCID 178429918HCID 178429918, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Trans-4-mercaptocyclohexanol (0.050 g), tris(dibenzylideneacetone)dipalladium(0) (0.008 g), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.010 g), and N,N-diisopropylethylamine (0.116 mL) were added to a solution of compound (40f) (0.150 g) prepared in Example 40(6) in 1,4-dioxane (1.71 mL), followed by stirring under nitrogen flow at 120° C. for 6 hr. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline. The organic layer after the washing was dried over anhydrous sodium sulfate, and the solvent was distilled away. The residue was purified by neutral silica gel column chromatography (n-hexane/ethyl acetate) to obtain a crude product of 2-(trans-4-hydroxycyclohexylthio)-4-{3-methyl-4-(quinolin-3-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl}benzonitrile. Subsequently, an aqueous sodium hydroxide solution (4 M, 0.851 mL) and a 30% hydrogen peroxide solution (0.193 mL) were added to a solution of this 2-(trans-4-hydroxycyclohexylthio)-4-{(3-methyl-4-(quinolin-3-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl}benzonitrile in DMSO (0.4 mL) and ethanol (1.6 mL) at room temperature, followed by stirring for 30 min. Water was added to the reaction solution, and the precipitate was collected by filtration, washed by sprinkling water and ether, and then dried under reduced pressure to obtain compound (67) (0.023 g, the second stage yield: 13%) as a white solid.

Workup

  1. washthe organic layer was washed with saturated saline
  2. dry with materialThe organic layer after the washing was dried over anhydrous sodium sulfate
  3. distillationthe solvent was distilled away
  4. customThe residue was purified by neutral silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a5ffc4d4f0f645fd8a4998512491e5a4
Source dataset
uspto-grants-2016_03
Patent number
US09273045B2

Reaction notes

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