Trifluoroacetic acid → HCID 68328510, compound

HRID 634170Notes

Reaction equation

HRID 634170 reaction equation
COC1C=CC(C[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]=[CH:35][CH:34]=3)=[N:11][N:10]=2)=CC=1.[OH-].[K+].COC1C=CC(CNC2SC(C3C=C4C(=CC=3)NC=C4C3N=C(N4CCN(C)C(=O)C4)C=CC=3)=NN=2)=CC=1.C(O)(C(F)(F)F)=O>O1CCOCC1.O>[NH2:8][C:9]1[S:13][C:12]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[NH:19][CH:18]=[C:17]3[C:33]2[N:38]=[C:37]([N:39]3[CH2:44][CH2:43][N:42]([CH3:45])[C:41](=[O:46])[CH2:40]3)[CH:36]=[CH:35][CH:34]=2)=[N:11][N:10]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 68328275HCID 68328275, compoundHCID 86725103HCID 86725103, compound

Product 1

HCID 68328510HCID 68328510, compoundYield 42.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °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)pyridin-2-yl)-1-methylpiperazin-2-one (350 mg, 0.515 mmol) in p-dioxane (6 mL) followed by aq. 1 M KOH (2.5 mL, 2.500 mmol). The reaction was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 80° C. for 15 min. The mixture was diluted with H2O and extracted with DCM. The combined organic layers were dried, filtered and concentrated to give the crude product. MS (ESI, pos. ion) m/z: 526 (M+1). A glass microwave reaction vessel was charged with crude 4-(6-(5-(5-(4-methoxybenzylamino)-1,3,4-thiadiazol-2-yl)-1H-indol-3-yl)pyridin-2-yl)-1-methylpiperazin-2-one (271 mg, 0.516 mmol) and TFA (5.00 mL, 67.3 mmol). The reaction was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 40 min, then the 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)pyridin-2-yl)-1-methylpiperazin-2-one (88.0 mg, 0.217 mmol, 42.1%). MS (ESI, pos. ion) m/z: 406 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.70 (1H, d, J=2.0 Hz), 8.79 (1H, d, J=1.6 Hz), 8.11 (1H, d, J=2.5 Hz), 7.71 (1H, dd, J=8.4, 1.8 Hz), 7.59 (1H, t, J=7.9 Hz), 7.50 (1H, d, J=8.6 Hz), 7.27 (2H, s), 7.22 (1H, d, J=7.4 Hz), 6.62 (1H, d, J=8.2 Hz), 4.12 (2H, s), 4.06 (2H, t, J=5.4 Hz), 3.58 (2H, t, J=5.3 Hz), 2.96 (3H, s).

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with DCM
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customA glass microwave reaction vessel
  8. stirringThe reaction was stirred
  9. temperatureheated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 40 min
  10. customthe solvent was removed
  11. customThe residue was purified with RP-HPLC

Sources & evidence

ORD record
ord-22708573e3e1481ab1116103895edbe7
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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