5-(Trifluoromethyl)pyrazin-2-amine → 5-(Trifluoromethyl)-6-(8-(5-(trifluoromethyl)pyrazin-2-ylamino)pyrido[2,3-b]pyrazin-3-yl)nicotinamide

HRID 545096Notes

Reaction equation

HRID 545096 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][C:8]([C:12]3[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)=[CH:9][N:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:25][C:26]1[CH:31]=[N:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=1>>[F:22][C:21]([F:24])([F:23])[C:20]1[C:12]([C:8]2[N:7]=[C:6]3[N:5]=[CH:4][CH:3]=[C:2]([NH:25][C:26]4[CH:31]=[N:30][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:28][N:27]=4)[C:11]3=[N:10][CH:9]=2)=[N:13][CH:14]=[C:15]([CH:19]=1)[C:16]([NH2:18])=[O:17]

Participants

3

Reactant 2

HCID 133411155-(Trifluoromethyl)pyrazin-2-amineHCID 671914016-(8-Chloropyrido[2,3-b]pyrazin-3-yl)-5-(trifluoromethyl)nicotinamide

Product 1

HCID 586457305-(Trifluoromethyl)-6-(8-(5-(trifluoromethyl)pyrazin-2-ylamino)pyrido[2,3-b]pyrazin-3-yl)nicotinamide

Procedure

Heat a mixture of 6-(8-chloropyrido[2,3-b]pyrazin-3-yl)-5-(trifluoromethyl)nicotinamide (70.6 mg, 0.2 mmol) and 2-amino-5-trifluoromethyl-pyrazine (98.4 mg, 0.6 mmol) in a screw cap vial at 140° C. for 20 hours under N2 atmosphere. Purify the reaction mixture by column chromatography using EtOAc to 1% MeOH/EtOAc as eluent to afford the title compound as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.182 (s, 1H), 9.456 (s, 1H), 9.44(s, 1H), 9.074 (d, 1H, J=1.3 Hz), 9.052 (s, 1H), 8.87(d, 1H, J=1.3 Hz), 8.828 (d, 1H, J=2.6 Hz), 8.542 (s, 1H), 7.974 (1, 1H). MS=481.42 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. temperatureHeat
  2. customcap vial at 140° C. for 20 hours under N2 atmosphere
  3. customPurify the reaction mixture by column chromatography

Sources & evidence

ORD record
ord-1a4b40c95961469699d3a2a5b7a62e99
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

Loading…