Chlorosuccinimide → HCID 86727198, compound

HRID 579375Notes

Reaction equation

HRID 579375 reaction equation
[S:1]1[C:5]([C:6]2[S:10][C:9]([N:11]([CH3:22])[CH:12]3[CH2:17][C:16]([CH3:19])([CH3:18])[NH:15][C:14]([CH3:21])([CH3:20])[CH2:13]3)=[N:8][N:7]=2)=[CH:4][C:3]2[CH:23]=[CH:24][CH:25]=[CH:26][C:2]1=2.[Cl:27]N1C(=O)CCC1=O>ClCCCl.CC(O)=O.C(=O)(O)[O-].[Na+]>[Cl:27][C:4]1[C:3]2[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=2[S:1][C:5]=1[C:6]1[S:10][C:9]([N:11]([CH3:22])[CH:12]2[CH2:17][C:16]([CH3:18])([CH3:19])[NH:15][C:14]([CH3:20])([CH3:21])[CH2:13]2)=[N:8][N:7]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 86727199HCID 86727199, compound

Product 1

HCID 86727198HCID 86727198, compoundYield 44.5%

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateSolventHCID 22609668HCID 22609668, compoundSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-(benzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (37 mg, 0.096 mmol) and N-chlorosuccinimide (15.34 mg, 0.115 mmol) in DCE:AcOH (1:1) (1 mL) was heated at 90° C. for six hours. The reaction was cooled to RT, diluted with saturated sodium bicarbonate, extracted with ethyl acetate (3×), and DCM (2×). The combined organic extracts were washed with brine, dried over magnesium sulfate and concentrated to a crystalline yellow solid. Purification by flash column chromatography (4 g silica gel, 1-17% 3.5 N ammonia in MeOH gradient in DCM over 30 column volumes) provided 5-(3-chlorobenzo[b]thiophen-2-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine as a yellow solid (18 mg). LC/MS Rt=0.58 min. MS=420.9 (M−1). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.84-7.99 (m, 2H), 7.47-7.60 (m, 2H), 4.53 (m, 1H), 3.14 (s, 3H), 1.83 (d, J=9.6 Hz, 2H), 1.55-1.68 (m, 2H), 1.38 (s, 6H), 1.26 (s, 6H).

Workup

  1. temperatureThe reaction was cooled to RT
  2. extractionextracted with ethyl acetate (3×), and DCM (2×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated to a crystalline yellow solid
  6. customPurification by flash column chromatography (4 g silica gel, 1-17% 3.5 N ammonia in MeOH gradient in DCM over 30 column volumes)

Sources & evidence

ORD record
ord-6f89ed4ffb9b47aeb1232a8b1046ae71
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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