Methyl chloroformate → HCID 68432778, compound

HRID 1046866Notes

Reaction equation

[NH2:1][C:2]1[N:31]=[C:5]2[N:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:7]([CH3:20])=[C:8]([C:18]#[N:19])[C@@H:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=3)[N:4]2[N:3]=1.C1COCC1.Cl[C:38]([O:40][CH3:41])=[O:39]>N1C=CC=CC=1>[CH3:41][O:40][C:38](=[O:39])[NH:1][C:2]1[N:31]=[C:5]2[N:6]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:30])[F:29])[CH:22]=3)[C:7]([CH3:20])=[C:8]([C:18]#[N:19])[C@@H:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=3)[N:4]2[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Under an atmosphere of argon protective gas, (7R)-2-amino-7-(4-cyanophenyl)-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (30 mg, 71 μmol) was dissolved in a mixture of abs. THF (3 ml) and abs. pyridine (57.5 μl). At room temperature, pyridine (5×57 μl) and methyl chloroformate (5×33.6 mg, 5×356 μmol; 25 eq.) were added in a plurality of portions. The mixture was then heated at 80° C. for 12 h. Once HPLC analysis showed substantial conversion, the reaction mixture was concentrated under reduced pressure and purified by preparative HPLC (Kromasil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (31.1 mg, 91% of theory).

Workup

concentrationthe reaction mixture was concentrated under reduced pressure
custompurified by preparative HPLC (Kromasil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
customAfter lyophilization, the product was obtained as a solid (31.1 mg, 91% of theory)

Sources & evidence

ORD record: ord-d47beb5027e24da8b101e6466b304599
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569314B2

Reaction notes

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