p-(Methylsulphonyl)benzoic acid → HCID 59451473, compound

HRID 1874802Notes

Reaction equation

HRID 1874802 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][S:31]([C:34]1[CH:42]=[CH:41][C:37]([C:38](O)=[O:39])=[CH:36][CH:35]=1)(=[O:33])=[O:32].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:38](=[O:39])[C:37]2[CH:36]=[CH:35][C:34]([S:31]([CH3:30])(=[O:33])=[O:32])=[CH:42][CH:41]=2)=[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 77670p-(Methylsulphonyl)benzoic acidHCID 81531DiisopropylethylamineHCID 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 59451473HCID 59451473, compoundYield 40.5%

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-(methylsulfonyl)benzoic acid (16.09 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 (0.016 g, 39%) as a white solid. 1H NMR (400 MHz, Acetone-d6): δ ppm 8.59 (t, 1H), 8.11-8.18 (m, 2H), 8.00-8.07 (m, 2H), 7.63 (t, 1H), 7.47-7.53 (m, 1H), 7.41-7.45 (m, 1H), 7.36-7.41 (m, 2H), 4.70 (d, 2H), 3.16 (s, 3H). LCMS m/z 494.9 (M+1).

Workup

  1. customPurification

Sources & evidence

ORD record
ord-dd3b3aeff4604e879003cba324017255
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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