Methyl iodide → Riociguat

HRID 346540Notes

Reaction equation

HRID 346540 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[N:15]=2)[N:3]=1.[H-].[Na+].I[CH3:34].[OH-].[K+]>O>[NH2:1][C:2]1[C:7]([N:8]([CH3:34])[C:9](=[O:12])[O:10][CH3:11])=[C:6]([NH2:13])[N:5]=[C:4]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[N:15]=2)[N:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 11690019Nelociguat

Product 1

HCID 11304743Riociguat

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Prepared in analogy to Example 6 with 310 mg (0.76 mmol) of methyl-4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate from Example 5, 27.32 mg (1.14 mmol) of sodium hydride and 215.5 mg (1.52 mmol) of iodomethane. The mixture is worked up by adding water and 2 molar potassium hydroxide solution and extracting with dichloromethane. The combined organic phases are dried with magnesium sulphate and concentrated in a rotary evaporator. The residue is purified by preparative RP-HPLC.

Workup

  1. extractionextracting with dichloromethane
  2. dry with materialThe combined organic phases are dried with magnesium sulphate
  3. concentrationconcentrated in a rotary evaporator
  4. customThe residue is purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-fd96cf9e406440569f1c3cd40e1f8e5b
Source dataset
uspto-grants-2007_02
Patent number
US07173037B2

Reaction notes

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