Nitrogen → HCID 69893792, compound

HRID 1356384Notes

Reaction equation

HRID 1356384 reaction equation
Br[C:2]1[C:3]2[CH:4]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18][CH:5]3[N:6](C(OC(C)(C)C)=O)[C:7]=2[CH:8]=[CH:9][CH:10]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[S:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[CH:40]=[C:39]1B(O)O.N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[S:38]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[CH:40]=[C:39]1[C:2]1[C:3]2[C@@H:4]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18][C@@H:5]3[NH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 62657Potassium Phosphate, TribasicHCID 69894587HCID 69894587, compound

Product 1

HCID 69893792HCID 69893792, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A 30-mL shaker vial was charged with di(tert-butyl) 10-bromo-1,2,4,5,5a,10b-hexahydroazepino[4,5-b]indole-3,6-dicarboxylate (0.10 g, 0.214 mmol), potassium phosphate (0.068 g, 0.32 mmol), benzothiophene-2-boronic acid (0.114 g, 0.642 mmol), and DMF (2 mL). The vial was purged with N2, and tetrakis(triphenylphosphine)palladium (0.025 g, 0.02 mmol) was added and the mixture was agitated at 250 RPM with heating at 80° C. overnight. The mixture was filtered through Celite, washing with MeOH (3-5 mL), and sulfonic acid resin (DOWEX®50W-X2, washed and dried, 4.8 meq/g dry weight) was added (1 g). The vial was then purged with N2, capped and agitated at 250 RPM with heating at 65° C. for 72 h. The mixture was filtered through a sintered funnel and the resin was washed 1:1 methylene chloride/methanol and then consecutively washed with MeOH and THF to ensure that all excess reagent was removed from the resin (the methanol and THF washes are alternated to swell and then shrink the resin to help expel reagents from inside the resin). The resin was then washed with 4M ammonium hydroxide in methanol (4×2 ml) and THF (2×2 ml) into an accurately weight round-bottomed flask. The filtrate was concentrated to give 0.040 g (68%) of an amber oil: MS (EI) m/z 321 (MH+); HPLC rt=3.68 min (100%).

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered through Celite
  3. washwashing with MeOH (3-5 mL), and sulfonic acid resin (DOWEX®50W-X2, washed and dried, 4.8 meq/g dry weight)
  4. additionwas added (1 g)
  5. customThe vial was then purged with N2
  6. customcapped
  7. stirringagitated at 250 RPM
  8. temperaturewith heating at 65° C. for 72 h
  9. filtrationThe mixture was filtered through a sintered funnel
  10. washthe resin was washed 1:1 methylene chloride/methanol
  11. washconsecutively washed with MeOH and THF
  12. customwas removed from the resin (the methanol and THF washes
  13. washThe resin was then washed with 4M ammonium hydroxide in methanol (4×2 ml) and THF (2×2 ml) into an accurately weight round-bottomed flask
  14. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-ba6f584c1ecd483c80b7768620d5a430
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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