Methyl chloroformate → HCID 70225630, compound

HRID 1046867Notes

Reaction equation

[NH2:1][C:2]1[N:35]=[C:5]2[N:6]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=3)[C:7]([CH3:24])=[C:8]([C:22]#[N:23])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][C:11]=3[S:18]([CH3:21])(=[O:20])=[O:19])[N:4]2[N:3]=1.C1COCC1.Cl[C:42]([O:44][CH3:45])=[O:43]>N1C=CC=CC=1>[CH3:45][O:44][C:42](=[O:43])[NH:1][C:2]1[N:35]=[C:5]2[N:6]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:32])[F:33])[CH:26]=3)[C:7]([CH3:24])=[C:8]([C:22]#[N:23])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][C:11]=3[S:18]([CH3:21])(=[O:20])=[O:19])[N:4]2[N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Under an atmosphere of argon protective gas, 2-amino-7-[4-cyano-2-(methylsulfonyl)phenyl]-5-methyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carbonitrile (7 mg, 13.6 μmol) was dissolved in a mixture of abs. THF (0.6 ml) and abs. pyridine (11 μl). At room temperature, abs. pyridine (5×11 μl) and methyl chloroformate (5×6.4 mg, 5×68.1 μmol; 25 eq.) were added in a plurality of portions. The mixture was then heated as 80° C. for 12 h. Once HPLC analysis showed substantial conversion, the reaction mixture was concentrated under reduced pressure and purified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA). After lyophilization, the product was obtained as a solid (5.4 mg, 69% of theory).

Workup

customAt room temperature
concentrationthe reaction mixture was concentrated under reduced pressure
custompurified by preparative HPLC (Gromsil C18 column, 30×250 mm; mobile phase: acetonitrile-water-0.1% TFA)
customAfter lyophilization, the product was obtained as a solid (5.4 mg, 69% of theory)

Sources & evidence

ORD record: ord-cb3d07cdd3b842b5bd82c85e611e2955
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569314B2

Reaction notes

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