Ammonium Chloride → HCID 68283778, compound

HRID 1630573Notes

Reaction equation

HRID 1630573 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-bea3ebe9ecd84832a981371999125034
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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