Acetic Acid → HCID 89923144, compound

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH:10]=O)[C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1.[NH:39]1[CH2:44][CH2:43][CH:42]([C:45]([OH:48])([CH3:47])[CH3:46])[CH2:41][CH2:40]1.CC(O)=O.C([BH3-])#N.[Na+]>>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH2:10][N:39]2[CH2:44][CH2:43][CH:42]([C:45]([OH:48])([CH3:47])[CH3:46])[CH2:41][CH2:40]2)[C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:32][CH2:33]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1

Participants

Reactant 4

HCID 176Acetic Acid

HCID 5003444Sodium cyanoborohydride

HCID 52003212-(4-Piperidyl)-2-propanol

HCID 89923126HCID 89923126, compound

Product 1

HCID 89923144HCID 89923144, compoundYield 70.7%

Procedure

2-((2-chloro-5-cyano-4-(3-oxopropyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (49 mg, 0.093 mmol) was taken up in TIIF (1 mL) and 2-(piperidin-4-yl)propan-2-ol (26.6 mg, 0.186 mmol), AcOH (5.32 μl, 0.093 mmol), and sodium cyanoborohydride (11.69 mg, 0.186 mmol) were added. The reaction was stirred at room temperature overnight. The reaction mixture was quenched with 2M K3PO4 solution and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-100% EtOAc/DCM then flushed with 10% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-4-(3-(4-(2-hydroxypropan-2-yl)piperidin-1-yl)propyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (43 mg) was obtained as a yellow glass.