Trifluoroacetic acid → 1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-8-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

HRID 1524439Notes

Reaction equation

HRID 1524439 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([C:37]1[S:41][N:40]=[CH:39][N:38]=1)[S:7]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([C:20]3[CH:21]=[CH:22][CH:23]=[C:24]4[C:29]=3[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]4)=[CH:15][N:16]2[CH3:19])=[CH:12][CH:11]=1)(=[O:9])=[O:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:19][N:16]1[C:17]2[C:13](=[CH:12][CH:11]=[C:10]([S:7]([NH:6][C:37]3[S:41][N:40]=[CH:39][N:38]=3)(=[O:8])=[O:9])[CH:18]=2)[C:14]([C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:29]=2[CH2:28][NH:27][CH2:26][CH2:25]3)=[CH:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71259294tert-butyl 8-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-methyl-1H-indol-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 712592211-methyl-3-(1,2,3,4-tetrahydroisoquinolin-8-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 8-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1-methyl-1H-indol-3-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.223 g, 0.330 mmol) was dissolved in 0.5 mL of DCM and TFA (0.1 ml, 1.298 mmol) was added. The reaction was stirred overnight at room temperature. The reaction was concentrated, dissolved in acetonitrile, and passed through a Biotage Isolute® PE-AX ion exchange column (Biotage AB, Uppsala, SE). The column was flushed several times with acetonitrile, then the product was liberated by flushing several times with an HCl solution in 15% MeOH/EtOAc. The resulting solution was concentrated. The material was redissolved in DCM and ethyl acetate and dried over magnesium sulfate. The solution was filtered and concentrated to afford 1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-8-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as a light pink solid. m/z (ESI) 427.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm=7.89 (s, 1 H), 7.79 (s, 1 H), 7.57 (br. s., 1 H), 7.48 (d, J=8.2 Hz, 1 H), 7.39 (d, J=8.7 Hz, 1 H), 7.29 (d, J=7.9 Hz, 1 H), 7.25-7.13 (m, 2 H), 3.99 (br. s., 1 H), 3.89 (s, 3 H), 2.99 (br. s., 2 H)

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in acetonitrile
  3. customThe column was flushed several times with acetonitrile
  4. customby flushing several times with an HCl solution in 15% MeOH/EtOAc
  5. concentrationThe resulting solution was concentrated
  6. dissolutionThe material was redissolved in DCM
  7. dry with materialethyl acetate and dried over magnesium sulfate
  8. filtrationThe solution was filtered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-bc0137fc019b40869f874cecc50539b4
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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