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 626615Notes

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 6A 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 title compound as a beige solid. The filtrate was re-concentrated, and purification by preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient) of the residue gave a further 180 mg (16% of theory) of the title 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
custompurification by preparative RP-HPLC (acetonitrile:water (+0.1% formic acid)−gradient) of the residue

Sources & evidence

ORD record: ord-c96e5e54b9804e6e8e0502579a9333dc
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309239B2

Reaction notes

Loading…