Diisopropylethylamine → N-[[4-chloro-3-(3-chloro-5-cyano-phenoxy)-2-fluoro-phenyl]methyl]-4-methyl-thiadiazole-5-carboxamide

HRID 1874801Notes

Reaction equation

HRID 1874801 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.CCN(C(C)C)C(C)C.[CH3:30][C:31]1[N:32]=[N:33][S:34][C:35]=1[C:36](O)=[O:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][C:36]([C:35]2[S:34][N:33]=[N:32][C:31]=2[CH3:30])=[O:37])=[C:4]([F:20])[C:5]=1[O:10][C:11]1[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([Cl:19])[CH:18]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 13819924-Methyl-1,2,3-thiadiazole-5-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 59451554N-[[4-chloro-3-(3-chloro-5-cyano-phenoxy)-2-fluoro-phenyl]methyl]-4-methyl-thiadiazole-5-carboxamideYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

In a 1 dram vial, 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 4-methyl-1,2,3-thiadiazole-5-carboxylic acid (11.58 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.014 g, 39%) as a white solid. 1H NMR (400 MHz, Acetone-d6): δ ppm 8.50 (br. s., 1H), 7.64 (t, 1H), 7.48-7.55 (m, 1H), 7.42-7.46 (m, 1H), 7.36-7.41 (m, 2H), 4.68 (d, 2H), 2.81-2.86 (m, 3H). LCMS m/z 436.8 (M+1).

Workup

  1. customPurification

Sources & evidence

ORD record
ord-56f5a97bebe846e7b255004833587f38
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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