Methyl chloroformate → Vericiguat

HRID 510035Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH2:17])[C:14]([NH2:18])=[C:13]([NH2:19])[N:12]=3)=[N:9][N:8]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:5]2=[N:6][CH:7]=1.Cl[C:29]([O:31][CH3:32])=[O:30]>N1C=CC=CC=1.ClCCl>[NH2:19][C:13]1[C:14]([NH:18][C:29](=[O:30])[O:31][CH3:32])=[C:15]([NH2:17])[N:16]=[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:8]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:9]=2)[N:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

31.75 g (86.20 mmol) of the compound from example 30A were initially charged in pyridine (600 ml) under argon and cooled to 0° C. Then a solution of 6.66 ml (86.20 mmol) of methyl chloroformate in dichloromethane (10 ml) was added dropwise and the mixture was stirred at 0° C. for 1 h. Thereafter, the reaction mixture was brought to RT, concentrated under reduced pressure and co-distilled repeatedly with toluene. The residue was stirred with water/ethanol and then filtered off with suction using a frit, and subsequently washed with ethanol and ethyl acetate. Subsequently, the residue was stirred again with diethyl ether, filtered off with suction and then dried under high vacuum.

Workup

customwas brought to RT
concentrationconcentrated under reduced pressure and co-distilled repeatedly with toluene
stirringThe residue was stirred with water/ethanol
filtrationfiltered off with suction
washsubsequently washed with ethanol and ethyl acetate
stirringSubsequently, the residue was stirred again with diethyl ether
filtrationfiltered off with suction
customdried under high vacuum

Sources & evidence

ORD record: ord-fe85ecb170c04e6d92a8c97deaa2e1ca
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096592B2

Reaction notes

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