Potassium Hydroxide → 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one

HRID 634144Notes

Reaction equation

HRID 634144 reaction equation
[CH3:1][O:2][C:3]1[CH:48]=[CH:47][C:6]([CH2:7][NH:8][C:9]2[S:13][C:12]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19](S(C3C=CC(C)=CC=3)(=O)=O)[CH:18]=[C:17]4[C:33]3[N:38]=[C:37]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[C:41](=[O:46])[CH2:40]4)[CH:36]=[N:35][CH:34]=3)=[N:11][N:10]=2)=[CH:5][CH:4]=1.[OH-].[K+]>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[S:13][C:12]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][CH:18]=[C:17]4[C:33]3[N:38]=[C:37]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[C:41](=[O:46])[CH2:40]4)[CH:36]=[N:35][CH:34]=3)=[N:11][N:10]=2)=[CH:47][CH:48]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 683280254-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one

Product 1

HCID 1212895394-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one (70 mg, 0.103 mmol) in THF (2 mL) followed by 1 M KOH (500 μL, 0.500 mmol). The mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 1 h, then cooled to RT. The mixture was diluted with H2O, and extracted with DCM. The combined organic layers were dried, filtered and concentrated to give the crude 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one. MS (ESI, pos. ion) m/z: 527 (M+1). A glass microwave reaction vessel was charged with the above crude compound (54 mg, 0.103 mmol) in TFA (1 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 30 min, then solvent was removed. The residue was purified with RP-HPLC to give 4-(6-(5-(5-amino-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyrazin-2-yl)-1-methylpiperazin-2-one (10.0 mg, 0.025 mmol, 24%) as a light yellow solid. MS (ESI, pos. ion) m/z: 407 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.86 (1H, br. s.), 8.73 (1H, s), 8.48 (1H, s), 8.28 (1H, d, J=2.5 Hz), 8.05 (1H, s), 7.74 (1H, dd, J=8.5, 1.5 Hz), 7.53 (1H, d, J=8.4 Hz), 7.26 (3H, s), 4.23 (2H, s), 4.06 (2H, t, J=5.4 Hz), 3.60 (2H, t, J=5.5 Hz), 3.28 (1H, s), 2.96 (3H, s)

Workup

  1. customA glass microwave reaction vessel
  2. temperaturecooled to RT
  3. extractionextracted with DCM
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-10f418a07ee44ab784aacb2d61f92d7e
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…