Methyl chloroformate → Vericiguat Impurity 100

HRID 1875457Notes

Reaction equation

HRID 1875457 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][C:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[N:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[C:16]([NH2:22])[N:15]=2)[N:6]=1.Cl[C:28]([O:30][CH3:31])=[O:29]>N1C=CC=CC=1>[CH3:31][O:30][C:28](=[O:29])[NH:21][C:17]1[C:16]([NH2:22])=[N:15][C:14]([N:7]2[C:8]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[C:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[F:1])=[N:6]2)=[N:19][C:18]=1[NH2:20]

Participants

4

Reactant 2

HCID 6586Methyl chloroformateHCID 24794429HCID 24794429, compound

Product 1

HCID 24794430Vericiguat Impurity 100

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

200 mg (0.57 mmol) of 2-[3-(2-fluorobenzyl)-1H-pyrazolo[4,3-b]pyridin-1-yl]pyrimidine-4,5,6-triamine from example 8 are dissolved in 10 ml of pyridine. The solution is cooled to 0° C., and 81 mg (0.86 mmol) of methyl chloroformate are added. The reaction mixture is stirred at RT overnight and then concentrated in vacuo, mixed with ethyl acetate and washed twice with water and with saturated sodium chloride solution. The organic phase is dried over sodium sulfate and concentrated in vacuo. The residue is purified by preparative HPLC to result in 125 mg (54% of theory) of the title compound as a pale beige solid.

Workup

  1. concentrationconcentrated in vacuo
  2. additionmixed with ethyl acetate
  3. washwashed twice with water and with saturated sodium chloride solution
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-d6e0e2c53cee4919a0bfd3950ffb96ee
Source dataset
uspto-grants-2012_11
Patent number
US08309551B2

Reaction notes

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