Ammonium Acetate → HCID 58215676, compound

HRID 1661713Notes

Reaction equation

HRID 1661713 reaction equation
C([O-])(=O)C.[NH4+:5].[C:6]([C:9]1[CH:10]=[C:11]([C:15]2[N:16]([CH3:27])[C:17]3[C:22]([C:23]=2[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([Cl:26])[CH:18]=3)[CH:12]=[N:13][CH:14]=1)(=[O:8])[CH3:7].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(OCC)(=O)C>[Cl:26][C:19]1[CH:18]=[C:17]2[C:22]([C:23]([C:24]#[N:25])=[C:15]([C:11]3[CH:12]=[N:13][CH:14]=[C:9]([CH:6]([OH:8])[CH3:7])[CH:10]=3)[N:16]2[CH3:27])=[CH:21][CH:20]=1.[NH2:5][CH:6]([C:9]1[CH:10]=[C:11]([C:15]2[N:16]([CH3:27])[C:17]3[C:22]([C:23]=2[C:24]#[N:25])=[CH:21][CH:20]=[C:19]([Cl:26])[CH:18]=3)[CH:12]=[N:13][CH:14]=1)[CH3:7]

Participants

7

Reactant 3

HCID 517165Ammonium AcetateHCID 5049666Sodium triacetoxyborohydride2×HCID 58215754HCID 58215754, compound

Product 2

HCID 58215676HCID 58215676, compoundHCID 67093894HCID 67093894, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

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 triphenyl 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. stirringthe reaction is stirred for 24 h at 50° C
  2. stirringthe reaction is stirred for another 24 h at 50° C
  3. washwashed with water thrice
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a771f5778f594e4891103ceadef59967
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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