Ammonium Chloride → HCID 68283778, compound

HRID 2408676Notes

Reaction equation

HRID 2408676 reaction equation
[N:1]([CH:4]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[CH2:5][N:6]1[C:14]2[CH:13]=[CH:12][C:11]([CH3:15])=[CH:10][C:9]=2[C:8]2[CH2:16][N:17]([CH3:20])[CH2:18][CH2:19][C:7]1=2)=[N+]=[N-].[Cl-].[NH4+]>C(O)C.O.[Zn]>[CH3:20][N:17]1[CH2:18][CH2:19][C:7]2[N:6]([CH2:5][CH:4]([C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[NH2:1])[C:14]3[CH:13]=[CH:12][C:11]([CH3:15])=[CH:10][C:9]=3[C:8]=2[CH2:16]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86677145HCID 86677145, compound

Product 1

HCID 68283778HCID 68283778, compoundYield 78.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-(2-azido-2-(4-fluorophenyl)ethyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g, 2.75 mmol) in ethanol-water (40-5 mL) was added ammonium chloride (590 mg, 11.02 mmol) and zinc dust (716 mg, 11.02 mmol) and heated at 100° C. for 1 h. After complete conversion of starting material (TLC), ethanol was removed under reduced pressure and 50 mL additional water was added and extracted with DCM (3×100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to obtain the crude product, which was purified by reverse phase HPLC to obtain 2-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(4-fluorophenyl)ethanamine (730 mg) as the TFA salt. 1H NMR (CD3OD, TFA salt): δ (ppm): 7.27 (m, 1H), 7.21 (m, 3H), 7.10 (m, 3H), 4.60 (m, 3H), 4.50 (m, 1H), 4.24 (m, 1H), 3.69 (m, 1H), 3.44 (m, 1H), 3.04 (m, 1H), 2.96 (s, 3H), 2.56 (m, 1H), 2.41 (s, 3H). Chiral HPLC separated the racemate into enantiomers II-11a-b.

Workup

  1. customAfter complete conversion of starting material (TLC), ethanol was removed under reduced pressure and 50 mL additional water
  2. additionwas added
  3. extractionextracted with DCM (3×100 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto obtain the crude product, which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-87ea7d3aeec742969c072c0344d321bd
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

Loading…