Ammonia → HCID 57474486, compound

HRID 552980Notes

Reaction equation

HRID 552980 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:37][Si](C)(C)C)(C)C.[Li+].N>C1COCC1.CO.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]>[O:17]1[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][CH2:11][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([NH2:37])[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 57474485HCID 57474485, compound

Product 1

HCID 57474486HCID 57474486, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To an argon purged vial fitted with a magnetic stirbar was charged a solution of compound 179 (407 mg, 1.26 mmol) in anhydrous THF (8 mL). The orange solution was treated with solid Pd2(dba)3 (58 mg, 0.063 mmol) which resulted in a dark red reaction mixture. Tri-t-butyl phosphine solution (10%, 0.37 mL, 0.13 mmol) was added and the reaction was stirred at room temperature for 5 minutes. A 1M solution of lithium bis(trimethylsily)amide in THF (3.78 mL, 3.78 mmol) was added, and the yellow-brown solution placed in a metal heating block and heated to reflux. The reaction was stirred at this temperature for 16 hours. TLC (10% 2M ammonia in methanol, 90% dichloromethane) revealed all starting material had reacted. The reaction was cooled to room temperature and quenched with 1M aqueous hydrogen chloride (15 mL). The acidic reaction was extracted with ethyl acetate (3×10 mL). The aqueous phase was basified with 3N sodium hydroxide (8 mL) and partitioned into ethyl acetate (3×10 mL). The organics were washed with brine, dried over magnesium sulfate, and treated with charcoal. Filtration through celite, concentration and further drying under high vacuum afforded a dark yellow oil. Purification of the product was performed using silica gel column chromatography (5-10% 2M ammonia in methanol, 95-90% dichloromethane) Yield: 102 mg of brown oil, compound 180 (31.2%). 1H NMR (CDCl3) δ 7.72 (br s, NH), 7.17-7.14 (d, 1H, J=8.4 Hz), 6.92-6.89 (dd, 2H, J=2.1, 4.5 Hz), 6.67-6.64 (dd, J=2.1, 8.4 Hz, 1H), 3.77-3.74 (t, J=4.5 Hz, 4H), 2.74-2.69 (t, J=7.5, 2H), 2.49-2.43 (m, 6H), 1.97-1.89 (m, 2H).

Workup

  1. customTo an argon purged vial fitted with a magnetic stirbar
  2. customresulted in a dark red reaction mixture
  3. temperatureheating block
  4. temperatureheated to reflux
  5. stirringThe reaction was stirred at this temperature for 16 hours
  6. customhad reacted
  7. temperatureThe reaction was cooled to room temperature
  8. customquenched with 1M aqueous hydrogen chloride (15 mL)
  9. customThe acidic reaction
  10. extractionwas extracted with ethyl acetate (3×10 mL)
  11. custompartitioned into ethyl acetate (3×10 mL)
  12. washThe organics were washed with brine
  13. dry with materialdried over magnesium sulfate
  14. additiontreated with charcoal
  15. filtrationFiltration
  16. concentrationthrough celite, concentration
  17. customfurther drying under high vacuum
  18. customafforded a dark yellow oil
  19. customPurification of the product

Sources & evidence

ORD record
ord-0fd9224759e945c8b13a45542957d161
Source dataset
uspto-grants-2011_05
Patent number
US07951940B2

Reaction notes

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