Ammonia → HCID 71007643, compound

HRID 1469506Notes

Reaction equation

HRID 1469506 reaction equation
[N:1]([CH:4]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][N:15]3[CH2:19][CH2:20][CH2:21][CH:14]3[C:13]=2[C:12]2[CH:11]=[C:10]([CH3:22])[CH:9]=[CH:8][C:7]1=2)=[N+]=[N-].[Cl-].[NH4+].N>C(O)C.O.[Zn]>[CH3:22][C:10]1[CH:9]=[CH:8][C:7]2[N:6]([CH2:5][CH:4]([NH2:1])[C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[C:18]3[CH2:17][CH2:16][N:15]4[CH2:19][CH2:20][CH2:21][CH:14]4[C:13]=3[C:12]=2[CH:11]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 86677143HCID 86677143, compound

Product 1

HCID 71007643HCID 71007643, compoundYield 10.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
80 °C

Procedure

6-(2-Azido-2-pyridin-4-yl-ethyl)-9-methyl-2,3,4,5,6,10c-hexahydro-1H-3a,6-diaza-cyclopenta[c]fluorene (400 mg, 1.07 mmol) was dissolved in ethanol-water (10 mL:1 mL). Zinc dust (280 mg, 4.3 mmol) and ammonium chloride (228 mg, 4.3 mmol) were added and the reaction mixture was heated at 80° C. for 1 h. After consumption of starting material, the reaction mixture was filtered through Celite and filtrate was concentrated to obtain the residue. The residue was basified with aq ammonia and extracted with EtOAc (2×100 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by reverse phase chromatography to obtain 40 mg of 2-(9-methyl-1,2,3,4,5,10c-hexahydro-3a,6-diaza-cyclopenta[c]fluoren-6-yl)-1-pyridin-4-yl-ethylamine as the TFA salt. 1H NMR (CDCl3, freebase): δ (ppm): 8.58 (d, 2H), 7.28 (d, 1H), 7.25 (s, 1H), 7.23 (d, 2H), 7.1 (d, 1H), 4.9 (m, 1H), 4.42 (t, 1H), 4.13 (dd, 1H), 3.63 (m, 1H), 3.4 (m, 2H), 3.01 (m, 2H), 2.71 (m, 2H), 2.45 (s, 3H), 2.23 (m, 2H), 2.01 (m, 1H). Chiral HPLC separated the racemate into diastereomers II-4a-d.

Workup

  1. customAfter consumption of starting material
  2. filtrationthe reaction mixture was filtered through Celite and filtrate
  3. concentrationwas concentrated
  4. customto obtain the residue
  5. extractionextracted with EtOAc (2×100 mL)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto obtain the crude product, which
  9. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-10e0d5c94380445fa828876c2a698b2f
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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