Potassium Carbonate → 5-(3-(6-(4-chlorophenyl)pyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine

HRID 634172Notes

Reaction equation

HRID 634172 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[S:21][C:20]([NH:22][CH2:23][C:24]5[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=5)=[N:19][N:18]=4)[CH:15]=3)[N:10]([S:32]([C:35]3[CH:41]=[CH:40][C:38]([CH3:39])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[CH:9]=2)[CH:5]=[CH:4][CH:3]=1.[Cl:42][C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:2]2[N:7]=[C:6]([C:8]3[C:16]4[C:11](=[CH:12][CH:13]=[C:14]([C:17]5[S:21][C:20]([NH:22][CH2:23][C:24]6[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=6)=[N:19][N:18]=5)[CH:15]=4)[N:10]([S:32]([C:35]4[CH:36]=[CH:37][C:38]([CH3:39])=[CH:40][CH:41]=4)(=[O:34])=[O:33])[CH:9]=3)[CH:5]=[CH:4][CH:3]=2)=[CH:45][CH:44]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 867251045-(3-(6-chloropyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 683280685-(3-(6-(4-chlorophenyl)pyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amineYield 83.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
105 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-(6-chloropyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine (245 mg, 0.407 mmol) and 4-chlorophenylboronic acid (95 mg, 0.610 mmol) in p-dioxane/H2O (4:1, 4.5 mL) followed by potassium carbonate (168 mg, 1.221 mmol) and Pd(PPh3)4 (23.5 mg, 0.020 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 105° C. for 30 min. The mixture was diluted with DCM and washed with H2O and separated. The organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-20% EtOAc in DCM) to give 5-(3-(6-(4-chlorophenyl)pyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine (230 mg, 0.339 mmol, 83%) as a light yellow solid. MS (ESI, pos. ion) m/z: 678 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.98 (1H, d, J=1.4 Hz), 8.15 (1H, s), 8.05-8.13 (3H, m), 7.98-8.03 (1H, m), 7.80-7.88 (3H, m), 7.66 (2H, d, J=8.2 Hz), 7.48 (2H, d, J=8.6 Hz), 7.33 (2H, d, J=8.6 Hz), 7.24 (2H, s), 6.89 (2H, d, J=8.6 Hz), 4.55 (2H, s), 3.80 (3H, s), 2.35 (3H, s).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with H2O
  3. customseparated
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with silica gel chromatography (eluting with 0-20% EtOAc in DCM)

Sources & evidence

ORD record
ord-1dca499940134eee8b6c030088aa1c65
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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