4-Methoxybenzenethiol → N-(6-(2-(4-methoxyphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide

HRID 2077492Notes

Reaction equation

HRID 2077492 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([SH:9])=[CH:5][CH:4]=1.Cl[C:11]1[N:16]=[C:15]([C:17]2[CH:29]=[CH:28][C:20]3[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=3[CH:18]=2)[CH:14]=[CH:13][N:12]=1>CN(C=O)C.[H-].[Na+]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:11]2[N:16]=[C:15]([C:17]3[CH:29]=[CH:28][C:20]4[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=4[CH:18]=3)[CH:14]=[CH:13][N:12]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 127654-MethoxybenzenethiolHCID 51357685N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide

Product 1

HCID 25182281N-(6-(2-(4-methoxyphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamideYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 24758Sodium hydrideSolvent

Procedure

4-Methoxythiophenol (0.168 ml, 1.36 mmol) was dissolved in DMF (1.0 mL) and NaH (60% in mineral oil), 66.8 mg, 1.67 mmol) was added. The reaction was stirred under nitrogen at RT for 65 minutes, then N-(6-(2-chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (48.0 mg, 158 μmol) was added, and the reaction solution was stirred overnight under nitrogen at RT and quenched with water. The suspension was filtered, and the solid was washed with water, MeOH, and Et2O, then collected. The layers of the biphasic filtrate were separated, and the aqueous phase was extracted with 10:1 DCM/MeOH (2×25 mL; 10 mL; 2×25 mL). Organic extracts were combined with the solid, concentrated, and purified on HPLC (10% to 95% MeCN/water with 0.1% TFA over 30 minutes) to afford N-(6-(2-(4-methoxyphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (24 mg, 38% yield). MS (ESI pos. ion) m/z: 409. Calculated exact mass for C20H16N4O2S2: 408. 1H NMR (400 MHz, DMSO-d6): 12.52 (s, 1H), 8.65 (s, 1H), 8.61 (d, J=8.5 Hz, 1H), 7.80 (m, 2H), 7.58 (d, J=8.5 Hz, 2H), 7.09 (d, J=8.5 Hz, 2H), 4.85 (s, 3H), 2.23 (s, 3H).

Workup

  1. stirringthe reaction solution was stirred overnight under nitrogen at RT
  2. customquenched with water
  3. filtrationThe suspension was filtered
  4. washthe solid was washed with water, MeOH, and Et2O
  5. customcollected
  6. customThe layers of the biphasic filtrate were separated
  7. extractionthe aqueous phase was extracted with 10:1 DCM/MeOH (2×25 mL; 10 mL; 2×25 mL)
  8. concentrationconcentrated
  9. custompurified on HPLC (10% to 95% MeCN/water with 0.1% TFA over 30 minutes)

Sources & evidence

ORD record
ord-6750b58ca19e4bad962f8eb37d604d07
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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