Trifluoroacetic acid → HCID 45138929, compound

HRID 1949089Notes

Reaction equation

HRID 1949089 reaction equation
C([N:8]1[C:20]2[C:19]([OH:21])=[C:18]3[N:22](C(OC(C)(C)C)=O)[C:23]4[CH:24]=[CH:25][C:26]([F:29])=[CH:27][C:28]=4[C:17]3=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[C:12]([F:37])[CH:13]=2)(OC(C)(C)C)=O.Cl.[CH3:39][N:40]([CH3:44])[CH2:41][CH2:42]Cl.C([O-])([O-])=O.[K+].[K+].FC(F)(F)C(O)=O>CC(C)=O>[F:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:18]1[C:19]([O:21][CH2:42][CH2:41][N:40]([CH3:44])[CH3:39])=[C:20]3[NH:8][C:9]4[CH:10]=[CH:11][C:12]([F:37])=[CH:13][C:14]=4[C:15]3=[CH:16][C:17]2=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 67212243HCID 67212243, compound

Product 1

HCID 45138929HCID 45138929, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 5,7-diBOC-2,10-difluoro-6-hydroxyindolo[2,3-b]carbazole (406.8 mg, 0.8 mmol), 2-(dimethylamino)ethyl chloride hydrochloride (126.8 mg, 0.88 mmol) and K2CO3 (10 equivalents) in 4A-molecular-sieve-dried acetone (40 mL) was magnetically stirred and heated to reflux under Ar. After the reaction was complete, it was cooled to room temperature. The inorganic salt was removed by filtration and washed with a small quantity of acetone. The combined acetone solution was concentrated on a rotavapor and dried under vacuum pump. The crude product was purified by flash chromatography. The resultant product 2-(2,10-difluoro-5,7-diBOC-indolo[2,3-b]carbazol-6-yloxy)-N,N-dimethylethanamine was dissolved in CH2Cl2 (40 mL), and trifluoroacetic acid (˜40 equivalents) was added. The reaction was stirred at room temperature overnight, concentrated, and dried under vacuum pump. The crude compound was dissolved in ethyl acetate (40 mL), washed with saturated NaHCO3 solution, dried under Na2SO4, concentrated, and flash chromatography to provide the desired product 2-(2,10-difluoro-5,7-dihydroindolo[2,3-b]carbazol-6-yloxy)-N,N-dimethylethanamine (195.9 mg, 65%). 1 H-NMR (400 MHz, DMSO-d6) δ ppm 11.40 (s, 2 H), 8.56 (s, 1 H), 7.87 (dd, J=9.2, 2.4 Hz, 2 H), 7.44 (dd, J=8.4, 4.4 Hz, 2 H), 7.20-7.11 (m, 2 H), 4.30 (t, J=5.8 Hz, 2 H), 2.72 (t, J=5.8 Hz, 2 H), 2.32 (s, 6 H); MS (ESI) m/z 378.1 (M−H)−; MS (ESI) m/z 380.1 (M+H)+

Workup

  1. temperatureheated
  2. temperatureto reflux under Ar
  3. customThe inorganic salt was removed by filtration
  4. washwashed with a small quantity of acetone
  5. concentrationThe combined acetone solution was concentrated on a rotavapor
  6. customdried under vacuum pump
  7. customThe crude product was purified by flash chromatography
  8. dissolutionThe resultant product 2-(2,10-difluoro-5,7-diBOC-indolo[2,3-b]carbazol-6-yloxy)-N,N-dimethylethanamine was dissolved in CH2Cl2 (40 mL)
  9. stirringThe reaction was stirred at room temperature overnight
  10. concentrationconcentrated
  11. customdried under vacuum pump
  12. dissolutionThe crude compound was dissolved in ethyl acetate (40 mL)
  13. washwashed with saturated NaHCO3 solution
  14. customdried under Na2SO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-71ff7daa990545e79c007473d676e38f
Source dataset
uspto-grants-2013_03
Patent number
US08399502B2

Reaction notes

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