Trifluoroacetic acid → HCID 71259291, compound

HRID 1524434Notes

Reaction equation

HRID 1524434 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=C(OC)C=CC=1C[N:26]([C:49]1[S:53][N:52]=[CH:51][N:50]=1)[S:27]([C:30]1[CH:38]=[C:37]2[C:33]([C:34](B3OC(C)(C)C(C)(C)O3)=[CH:35][N:36]2[CH3:39])=[CH:32][CH:31]=1)(=[O:29])=[O:28].C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:34]2[C:33]3[C:37](=[CH:38][C:30]([S:27]([NH:26][C:49]4[S:53][N:52]=[CH:51][N:50]=4)(=[O:28])=[O:29])=[CH:31][CH:32]=3)[N:36]([CH3:39])[CH:35]=2)=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:3]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 27733975-Bromo-2-iodobenzotrifluorideHCID 71259251N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide2×

Product 1

HCID 71259291HCID 71259291, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

A vial containing 4-bromo-1-iodo-2-(trifluoromethyl)benzene was charged with potassium phosphate (0.130 g, 0.614 mmol), followed by a solution of N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate H) (0.100 g, 0.175 mmol) and PdCl2(dppf)-CH2Cl2 (0.014 g, 0.018 mmol) in 1 mL of DMF. The vial was sealed and placed in a shaker block. The block was shaken for three hours at 85° C. The solution was filtered, washed with DMF and concentrated. The resulting solid was treated with a solution of TFA (0.270 mL, 3.51 mmol) in 1 mL of DCM. The vial was shaken at room temperature for two hours. The solution was concentrated and purified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier) to afford 3-(4-bromo-2-(trifluoromethyl)phenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 3.95 (s, 3 H) 7.40-7.51 (m, 3 H) 7.69 (s, 1 H) 7.92-8.00 (m, 2 H) 8.03 (d, J=1.95 Hz, 1 H) 8.40 (s, 1 H). m/z (ESI) 515.9 (M+H)+.

Workup

  1. customThe vial was sealed
  2. filtrationThe solution was filtered
  3. washwashed with DMF
  4. concentrationconcentrated
  5. stirringThe vial was shaken at room temperature for two hours
  6. concentrationThe solution was concentrated
  7. custompurified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier)

Sources & evidence

ORD record
ord-0cbd11db69904b36888e233dd037d2c4
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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