Sodium Hydroxide → 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine

HRID 634259Notes

Reaction equation

HRID 634259 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:24][N:23]=[C:22]([NH2:25])[N:21]=4)[CH:18]=3)[N:13]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH:12]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2].[OH-].[Na+].O1[CH2:43][CH2:42][O:41][CH2:40]C1>>[CH:1]([NH:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:24][N:23]=[C:22]([NH:25][CH2:19][C:11]5[CH:12]=[CH:43][C:42]([O:41][CH3:40])=[CH:8][CH:9]=5)[N:21]=4)[CH:18]=3)[N:13]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=3)(=[O:27])=[O:28])[CH:12]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 683288335-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine

Product 1

HCID 683286605-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amineYield 20%

Conditions

Temperature
100 °C

Procedure

To a solution of 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (0.5 g, 0.99 mmol) in 1,4-dioxane (5 mL) was added 10% aq NaOH (2.5 mL) and the reaction was heated at 100° C. for 2 hr. The mixture was cooled to RT and was treated with ice cold water to give off white precipitate. The precipitate was filtered and washed with ice cold water and further purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in water with 0.01% TFA) to give 5-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (70 mg, 20%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 11.96 (s, 1H), 9.05 (d, J=1.2 Hz, 1H), 8.27 (m, 2H), 7.78 (d, J=8.4 Hz, 1H), 7.67 (m, 2H), 7.59 (d, J=8.4 Hz, 1H), 7.20 (m, 1H), 4.61 (m, 1H), 1.32 (d, J=6.4 Hz, 6H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. additionwas treated with ice cold water
  3. customto give off white precipitate
  4. filtrationThe precipitate was filtered
  5. washwashed with ice cold water
  6. customfurther purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in water with 0.01% TFA)

Sources & evidence

ORD record
ord-4d02087d71b64ec69a17411e3968bd16
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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