Diisopropylethylamine → N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-methyl-2H-1,2,3-triazole-4-carboxamide

HRID 1874978Notes

Reaction equation

HRID 1874978 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[CH3:45][C:46]1[C:47]([C:51](O)=[O:52])=[N:48][NH:49][N:50]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:51]([C:47]2[C:46]([CH3:45])=[N:50][NH:49][N:48]=2)=[O:52])=[C:28]([F:44])[C:29]=1[O:34][C:35]1[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 44360405-methyl-2H-1,2,3-triazole-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 59451546N-({4-Chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-methyl-2H-1,2,3-triazole-4-carboxamideYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.092 g, 0.241 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol), 5-methyl-2H-1,2,3-triazole-4-carboxylic acid (0.022 g, 0.177 mmol) and DIPEA (0.042 mL, 0.241 mmol) in DMF (2 mL). The resulting solution was stirred overnight. The reaction mixture was partitioned between water and EtOAc. The organic layer was separated, dried over MgSO4 and evaporated to a residue. Purification was accomplished by reverse-phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.0191 g, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.51 (s, 1H), 7.79 (d, 1H), 7.69 (t, 1H), 7.46-7.51 (m, 2H), 7.44 (d, 1H), 7.30 (t, 1H), 4.36 (d, 2H), 2.15 (s, 3H). LCMS: m/z 420.0 (M+1).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated to a residue
  5. customPurification

Sources & evidence

ORD record
ord-7547c531244546b4b4dab2b9796d1684
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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