Chloroform → HCID 58087997, compound

HRID 1875878Notes

Reaction equation

HRID 1875878 reaction equation
N1(C(=S)NC2[S:9][C:10]3[CH:16]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[CH:14]=[CH:13][C:11]=3[N:12]=2)C=CN=C1.[CH2:22]([N:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[CH3:23].[CH:29]([N:32]=C=NC(C)C)(C)C.[CH:38](Cl)(Cl)Cl.C[N:43]([CH3:46])[CH:44]=[O:45]>O>[N:24]12[CH2:27][CH2:28][CH:38]([CH2:26][CH2:25]1)[C@@:23]1([O:45][C:44]([NH:43][C:46]3[S:9][C:10]4[CH:16]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[CH:14]=[CH:13][C:11]=4[N:12]=3)=[N:32][CH2:29]1)[CH2:22]2

Participants

7

Reactant 5

HCID 6212ChloroformHCID 6228DimethylformamideHCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 58088193HCID 58088193, compound

Product 1

HCID 58087997HCID 58087997, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To N-(2-(1H-imidazole-1-carbothioamido)benzo[d]thiazol-6-yl)acetamide (300 mg, 0.95 mmol) in N,N-dimethylformamide (10 mL) was added (S)-3-(aminomethyl)quinuclidin-3-ol, 2HCl (238 mg, 1 mmol) and triethylamine (0.39 mL, 2.84 mmol). The reaction was heated to 80° C. for 3 hours. N,N′-diisopropylcarbodiimide (0.59 mL, 3.78 mmol) was then added to the reaction mixture. The mixture was heated at 80° C. for another 2 hours. The reaction was cooled, then chloroform and water were added to the mixture. The organic layer concentrated in vacuo to yield crude product. The crude material was purified via flash chromatography (2-20% [10% ammonium hydroxide/methanol-chloroform). The product fractions were then triturated with ether to yield (R)—N-(2-(4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]-2-ylamino)benzo[d]thiazol-6-yl)acetamide (144.5 mg, 0.39 mmol, 41.2% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.98 (1H, s), 8.93 (1H, br. s.), 8.12 (1H, d, J=1.83 Hz), 7.52 (1H, d, J=8.42 Hz), 7.38 (1H, dd, J=8.60, 2.01 Hz), 3.88 (1H, d, J=9.88 Hz), 3.62 (1H, d, J=9.88 Hz), 3.02 (2H, s), 2.74-2.85 (2H, m), 2.66 (2H, t, J=7.68 Hz), 2.05 (4H, s), 1.91 (1H, br. s.), 1.41-1.64 (3H, m). MS (LC/MS) R.T.=1.55; [M+H]+=372.2.

Workup

  1. temperatureThe mixture was heated at 80° C. for another 2 hours
  2. temperatureThe reaction was cooled
  3. concentrationThe organic layer concentrated in vacuo
  4. customto yield crude product
  5. customThe crude material was purified via flash chromatography (2-20% [10% ammonium hydroxide/methanol-chloroform)
  6. customThe product fractions were then triturated with ether

Sources & evidence

ORD record
ord-940ebc4c90774daa9c9850cd9b3bb706
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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