Ammonium Chloride → HCID 68283832, compound

HRID 1469466Notes

Reaction equation

HRID 1469466 reaction equation
[N:1]([CH:4]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=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][CH2:17][N:18]([CH3:21])[CH2:19][CH2:20][C:7]1=2)=[N+]=[N-].[Cl-].[NH4+]>C(O)C.O.[Zn]>[CH3:21][N:18]1[CH2:17][CH2:16][C:8]2[C:9]3[CH:10]=[C:11]([CH3:15])[CH:12]=[CH:13][C:14]=3[N:6]([CH2:5][CH:4]([C:22]3[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=3)[NH2:1])[C:7]=2[CH2:20][CH2:19]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86677142HCID 86677142, compound

Product 1

HCID 68283832HCID 68283832, compoundYield 25.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 6-(2-azido-2-(pyridin-4-yl)ethyl)-3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (188 mg, 0.522 mmol) in ethanol-water (9 mL: 1 mL), zinc dust (135 mg, 2.08 mmol) and ammonium chloride (110 mg, 2.08 mmol) were added and the reaction mixture was stirred at 85° C. for 45 min. The reaction mixture was filtered and the filtrate concentrated. The residue was basified with aqueous ammonia and extracted with EtOAc (2×50 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude material was purified by reverse phase HPLC to yield 2-(3,9-dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-1-(pyridin-4-yl)ethanamine (45 mg). The racemate can be further separated into the optically active forms by chiral preparative HPLC. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.6 (d, 2H), 7.6 (d, 2H), 7.22 (s, 1H), 7.0 (s, 1H), 6.9 (s, 1H), 4.9 (m, 3H), 4.8 (m, 1H), 4.7 (m, 1H), 3.8-3.6 (m, 2H), 3.2 (m, 2H), 3.18-2.97 (m, 4H), 2.8 (bs, 1H), 2.38 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate concentrated
  3. extractionextracted with EtOAc (2×50 mL)
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-69e2b4e330674fca9a923aa75a85599d
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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