Potassium Cyanide → 4-(6-cyano-5-(2,3-difluorobenzylamino)-1,2,4-triazin-3-ylamino)-N,N-dimethylbenzamide

HRID 577428Notes

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([NH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[CH:11][CH:10]=2)=[N:4][C:3]=1[NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:23]=1[F:29].[C-:30]#[N:31].[K+].C1OCCOCCOCCOCCOCCOC1>CN1C(=O)CCC1>[C:30]([C:2]1[N:7]=[N:6][C:5]([NH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[CH:11][CH:10]=2)=[N:4][C:3]=1[NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:23]=1[F:29])#[N:31]

Participants

Conditions

Temperature: 130 °C

Procedure

4-(6-Chloro-5-(2,3-difluorobenzylamino)-1,2,4-triazin-3-ylamino)-N,N-dimethylbenzamide (20 mg) was dissolved in 2 mL NMP. To it was added KCN (100 mg) and 18-crown-6 (20 mg). The mixture was stirred in a sealed tube at 130° C. for overnight. It was cooled to RT and subjected to reverse phase preparative HPLC to isolate the cyanation product, 4-(6-cyano-5-(2,3-difluorobenzylamino)-1,2,4-triazin-3-ylamino)-N,N-dimethylbenzamide. It was dissolved in 2 mL DMSO and 10 mL methanol. To it was added 100 mg KOH and then 1 mL H2O2 (50%). The mixture was stirred at RT for 1 h. It was treated with acetonitrile and TFA, concentrated and subjected to reverse phase preparative HPLC to isolate the title compound (3 mg). MS found for C20H19F2N7O2 as (M+H)+ 428.3. UV: λ=244, 278 nm. Proton NMR: (CD3OD) δ 7.53 (2H, d, J=8.8 Hz), 7.43 (2H, d, J=8.4 Hz), 7.20 (1H, m), 7.14-7.11 (2H, m), 4.84 (2H, s), 3.11 (3H, s), 3.04 (3H, s) ppm.

Workup

temperatureIt was cooled to RT

Sources & evidence

ORD record: ord-a49d3cdf11b64238b149152fde516790
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040530B2

Reaction notes

Loading…