Trifluoroacetic acid → 5-(benzylamino)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

HRID 1473426Notes

Reaction equation

HRID 1473426 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([N:15](CC1C=CC(OC)=CC=1OC)[C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH2:74]([NH2:81])[C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1.C(O)(C(F)(F)F)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH2:74]([NH:81][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([S:12]([NH:15][C:16]1[S:20][N:19]=[CH:18][N:17]=1)(=[O:14])=[O:13])=[CH:7]2)[C:75]1[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7504BenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866873455-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide2×

Product 1

HCID 715866075-(benzylamino)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with 5-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (Intermediate D, 0.100 g, 0.192 mmol), Pd2(dba)3 (0.018 g, 0.019 mmol), Xantphos (0.022 g, 0.038 mmol), and toluene (1.922 ml). Benzylamine (0.042 ml, 0.384 mmol) was added and the reaction was stirred for one hour at 100° C. The reaction was filtered through a plug of diatomaceous earth, which was then washed with ethyl acetate. The filtrate was concentrated, dissolved in 1 mL of DCM, and TFA (0.1 ml, 1.298 mmol) was added. The reaction was concentrated and purified via HPLC (50-95% MeCN:H2O with 0.1% TFA modifier) to afford 5-(benzylamino)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.48 (s, 1H), 8.42 (d, J=9.1 Hz, 1H), 8.28 (d, J=2.0 Hz, 1H), 7.70 (dd, J=2.0, 9.0 Hz, 1H), 7.39 (d, J=7.6 Hz, 2H), 7.34-7.27 (m, 4H), 7.24-7.17 (m, 1H), 6.51 (dd, J=2.2, 6.6 Hz, 1H), 4.50 (s, 2H). m/z (ESI) 397.3 (M+H)+.

Workup

  1. filtrationThe reaction was filtered through a plug of diatomaceous earth, which
  2. washwas then washed with ethyl acetate
  3. concentrationThe filtrate was concentrated
  4. dissolutiondissolved in 1 mL of DCM
  5. concentrationThe reaction was concentrated
  6. custompurified via HPLC (50-95% MeCN:H2O with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-1ab2f12cfacd4cc09d66c11147b91f02
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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