Ammonium Chloride → (R)-N-methyl-N-(1-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-amine

HRID 527923

Reaction equation

HRID 527923 reaction equation
[CH3:1][N:2]([C@@H:13]1[CH2:17][CH2:16][N:15]([C:18]2[C:19]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:14]1)[C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([N+:10]([O-])=O)=[CH:5][N:4]=1.[NH4+].[Cl-].[N:37]([O-])=O.[Na+].N.O>C(O)C.O.[Fe]>[CH3:1][N:2]([C@@H:13]1[CH2:17][CH2:16][N:15]([C:18]2[C:19]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:14]1)[C:3]1[CH:8]=[C:7]2[CH:9]=[N:37][NH:10][C:6]2=[CH:5][N:4]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 12896473Azane;hydrateHCID 23668193Sodium NitriteHCID 86692145(R)-N,4-dimethyl-5-nitro-N-(1-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)pyridin-2-amine

Product 1

HCID 86692146(R)-N-methyl-N-(1-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-amineYield 33%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of (R)—N,4-dimethyl-5-nitro-N-(1-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl)pyridin-2-amine (0.248 mmol) in ethanol (20 mL) and water (5 mL), was added iron powder (0.752 mmol) and NH4Cl (1.495 mmol). The mixture was stirred at refluxing temperature for 2 hours, cooled, and filtered. The filtrate was concentrated, and dissolved in CH3COOH (1.5 mL) and water (2.5 mL). NaNO2 (0.304 mmol) was then slowly added, and the mixture was stirred at room temperature overnight, which was subsequently treated with NH3.H2O and extracted with EtOAc (3×20 mL). The combined extracts were concentrated and the residue was purified by column chromatography to give the title compound in 33.0% yield.

Workup

  1. temperatureat refluxing temperature for 2 hours
  2. temperaturecooled
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. dissolutiondissolved in CH3COOH (1.5 mL)
  6. stirringthe mixture was stirred at room temperature overnight
  7. extractionextracted with EtOAc (3×20 mL)
  8. concentrationThe combined extracts were concentrated
  9. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-fd5238fc5b804296bb3e0cf629c60fe6
Source dataset
uspto-grants-2016_05
Patent number
US09346810B2

Linked notes

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