Methyl chloroformate → Methyl {4,6-diamino-2-[6-fluoro-3-(2-fluorobenzyl)-1H-pyrazolo [4,3-b]pyridin-1-yl]pyrimidin-5-yl}carbamate

HRID 1528678Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[N:16]=[C:15]([NH2:17])[C:14]([NH2:18])=[C:13]([NH2:19])[N:12]=3)[N:9]=[C: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>[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]([N:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[C: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

Under argon, 1.00 g (2.72 mmol) of the compound from example 8A was initially charged in pyridine (55 ml), the mixture was cooled to 0° C. and 228 μl (2.72 mmol) of methyl chloroformate (solution in 10 ml of dichloromethane) were then added dropwise. The reaction mixture was stirred further at RT overnight and then concentrated. The residue was triturated with ethanol and the solid was filtered off and dried at 50° C. under high vacuum. This gave 873 mg (75% of theory) of the target compound as a solid. The filtrate was re-concentrated, and preparative RP-HPLC (acetonitrile:water (+0.1% formic acid) gradient) of the residue gave a further 180 mg (16% of theory) of the target compound.

Workup

concentrationconcentrated
customThe residue was triturated with ethanol
filtrationthe solid was filtered off
customdried at 50° C. under high vacuum
concentrationThe filtrate was re-concentrated
custompreparative RP-HPLC (acetonitrile:water (+0.1% formic acid) gradient) of the residue gave a further 180 mg (16% of theory) of the target compound

Sources & evidence

ORD record: ord-93d00c0099c14445b13de192246ab607
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090609B2

Reaction notes

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