Hydrochloric Acid → HCID 58215676, compound

HRID 1630939Notes

Reaction equation

HRID 1630939 reaction equation
C1(=O)NC(=O)C2=CC=CC=C12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:31][C:32]1[CH:40]=[C:39]2[C:35]([C:36]([C:61]#[N:62])=[C:37]([C:42]3[CH:43]=[N:44][CH:45]=[C:46]([CH:48]([N:50]4C(=O)C5C(=CC=CC=5)C4=O)[CH3:49])[CH:47]=3)[N:38]2[CH3:41])=[CH:34][CH:33]=1.P.O.NN.Cl>C1COCC1.C(OCC)(=O)C.C(O)C>[NH2:50][CH:48]([C:46]1[CH:47]=[C:42]([C:37]2[N:38]([CH3:41])[C:39]3[C:35]([C:36]=2[C:61]#[N:62])=[CH:34][CH:33]=[C:32]([Cl:31])[CH:40]=3)[CH:43]=[N:44][CH:45]=1)[CH3:49]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 24404PhosphineHCID 24654Hydrazine hydrate (1:1)HCID 67093639HCID 67093639, compound

Product 1

HCID 58215676HCID 58215676, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ammonium acetate (0.567 g, 7.207 mmol) is added to a solution of 2-(5-acetyl-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile (0.470 g, 1.441 mmol) in MeOH (10 mL), and the reaction is stirred at 50° C. for 48 h. Sodium triacetoxyborohydride (2.251 g, 10.09 mmol) is added and the reaction is stirred for 24 h at 50° C. Additional sodium triacetoxyborohydride (2.251 g, 10.09 mmol) is added and the reaction is stirred for another 24 h at 50° C. It is then diluted with ethyl acetate and washed with water thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo to give 6-chloro-2-[5-(1-hydroxy-ethyl)-pyridin-3-yl]-1-methyl-1H-indole-3-carbonitrile and minor amounts of 2-[5-(1-amino-ethyl)-pyridin-3-yl]-6-chloro-1-methyl-1H-indole-3-carbonitrile. The mixture is redissolved in THF (5 mL) and phthalimide (0.181 g, 1.206 mmol) and triphenylphosphine (0.172 g, 0.804 mmol) are added, followed with di-isopropylazodicarboxylate (0.157 mL, 0.804 mmol). The reaction is stirred at room temperature for 4 h. It is then diluted with ethyl acetate and washed with water thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo, to give a residue which is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:1) to afford a mixture of 6-chloro-2-{5-[1-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-pyridin-3-yl}-1-methyl-1H-indole-3-carbonitrile and triphehyl phosphine. The mixture is redissolved in ethanol (5 mL). Hydrazine hydrate (65%) (0.411 mL, 8.506 mmol) is added and the reaction is stirred at room temperature overnight. It is then acidified with 2M aqueous HCl and concentrated in vacuo. The residue is redissolved in dichloromethane and filtered through celite to remove the precipitate formed. The organic layer is washed with water. The aqueous layer is separated and basified to with 4M aqueous NaOH, and then extracted with dichloromethane thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo to afford 2-[5-(1-amino-ethyl)-pyridin-3-yl]-6-chloro-1-methyl-1H-indole-3-carbonitrile as a solid. MS (ESI) m/z 311.1 (M+H)+

Workup

  1. washwashed with water thrice
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a residue which
  5. customis purified by silica gel flash chromatography (heptane-ethyl acetate, 1:1)
  6. customto afford
  7. stirringthe reaction is stirred at room temperature overnight
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue is redissolved in dichloromethane
  10. filtrationfiltered through celite
  11. customto remove the precipitate
  12. customformed
  13. washThe organic layer is washed with water
  14. customThe aqueous layer is separated
  15. extractionextracted with dichloromethane thrice
  16. dry with materialThe organic layer is dried over sodium sulfate
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b48a970831cb4c0884271a59993237e3
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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