Ammonium Hydroxide → HCID 178423697, compound

HRID 2047560Notes

Reaction equation

HRID 2047560 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([C@H:10]3[CH2:13][C@H:12]([N:14]4[CH2:18][CH2:17][CH2:16][CH:15]4[CH3:19])[CH2:11]3)=[N:7][C:6]=2[CH:20]=1.[F-].[K+].[CH3:23][C:24]1[C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=[C:26]([CH3:39])[N:25]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[OH-].[NH4+]>ClCCl.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].CO.O1CCOCC1>[CH3:23][C:24]1[C:29]([C:2]2[CH:3]=[CH:4][C:5]3[S:9][C:8]([C@H:10]4[CH2:13][C@H:12]([N:14]5[CH2:18][CH2:17][CH2:16][CH:15]5[CH3:19])[CH2:11]4)=[N:7][C:6]=3[CH:20]=2)=[CH:28][CH:27]=[C:26]([CH3:39])[N:25]=1

Participants

10

Reactant 5

HCID 14923Ammonium HydroxideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 219800342,6-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 178426207HCID 178426207, compound

Product 1

HCID 178423697HCID 178423697, compoundYield 16.2%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

In a 4 ml vial, the product of Example 91E (30 mg, 0.098 mmole), potassium fluoride (19 mg, 0.323 mmole) and tris(dibenzylideneacetone)dipalladium (5.3 mg, 0.0075 mmole) were charged and dried on high vacuum for 30 min. The product of Example 2A (34 mg, 0.147 mmole) was added followed by dioxane (1 ml) under nitrogen atmosphere. Tri-t-butylphosphine (10 wt % in hexane, 45 ul, 0.0147 mmole) was added last and the vial was sealed and heated at 85° C. overnight then 95° C. for 7 h. TLC (TLC conditions: 1% ammonium hydroxide and 10% methanol in dichloromethane on silica gel) showed a new spot besides the starting material. The reaction mixture was quenched with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane) to give 6 mg (16% yield) of title compound. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 7.93 (d, J=1.36 Hz, 1H), 7.89 (d, J=8.14 Hz, 1H), 7.47 (d, J=7.80 Hz, 1H), 7.30 (dd, J=8.48, 1.70 Hz, 1H), 7.08 (d, J=7.80 Hz, 1H), 3.80-3.94 (m, 1H), 3.46-3.60 (m, 1H), 3.02-3.15 (m, 1H), 2.66-2.84 (m, 3H), 2.60-2.61 (s, 3H), 2.50-2.54 (s, 3H), 2.26-2.40 (m, 2H), 1.62-2.04 (m, 4H), 1.43-1.58 (m, 1H), 1.15 (d, J=5.76 Hz, 3H). (M+H)+=378.

Workup

  1. customdried on high vacuum for 30 min
  2. customthe vial was sealed
  3. customThe reaction mixture was quenched with water
  4. extractionextracted three times with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7017924f2adf472882f7b6450cb7b0e7
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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