Diisopropylethylamine → (cis)-N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide

HRID 1922032Notes

Reaction equation

HRID 1922032 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH:13]([C:17]([OH:19])=O)[CH2:12]2)[N:3]=1.[NH2:20][CH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][C:23]=1[C:30]([F:33])([F:32])[F:31].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[C:26]([C:25]1[CH:28]=[CH:29][C:22]([CH2:21][NH:20][C:17]([C@H:13]2[CH2:14][CH2:15][CH2:16][C@@H:11]([NH:10][C:4]3[N:3]=[C:2]([CH3:1])[N:7]=[C:6]([NH:8][CH3:9])[N:5]=3)[CH2:12]2)=[O:19])=[C:23]([C:30]([F:31])([F:33])[F:32])[CH:24]=1)#[N:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 594482213-{[4-Methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxylic acidHCID 673396874-(Aminomethyl)-3-(trifluoromethyl)benzonitrile

Product 1

HCID 67493453(cis)-N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamideYield 56.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxylic acid (0.100 g, 0.264 mmol) in N,N-Dimethylformamide (DMF) (4 ml) was added 4-(aminomethyl)-3-(trifluoromethyl)benzonitrile (0.053 g, 0.264 mmol) followed by diisopropylethylamine (0.101 ml, 0.580 mmol) and 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.128 g, 0.290 mmol). The reaction was stirred at room temperature for 4 hours and then purified by preparative HPLC to provide (cis)-N-{[4-cyano-2-(trifluoromethyl)phenyl]methyl}-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (83 mg, 0.148 mmol, 56%). MS (ES) m/e 448 [M+H]+. 1H NMR (400 MHz, DMSO-D6) □ 7.8 (bs, 1H), 7.3 (bs, 1H), 7.2 (m, 1H), 6.9 (m, 1H), 3.8 (bs, 2H), 3.3 (bm, 1H), 2.2 (bm, 4H), 1.8-1.5 (bm, 4H), 1.3-1.1 (bm, 4H), 0.8-0.5 (bm, 4H)

Workup

  1. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-0f817dd8f25945ddb01b5b2fbd8cf5b5
Source dataset
uspto-grants-2012_05
Patent number
US08173805B2

Reaction notes

Loading…