Benzylamine → Aplindore

HRID 1259453Notes

Reaction equation

HRID 1259453 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:26][C:17]3=[C:18]4[C:22](=[CH:23][CH:24]=[C:16]3[O:15][CH2:14]2)[NH:21][C:20](=[O:25])[CH2:19]4)(=O)=O)=CC=1.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CS(C)=O>[CH2:27]([NH:34][CH2:12][C@@H:13]1[O:26][C:17]2=[C:18]3[C:22](=[CH:23][CH:24]=[C:16]2[O:15][CH2:14]1)[NH:21][C:20](=[O:25])[CH2:19]3)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 7504BenzylamineHCID 15381104(R)-2-(Toluene-4-sulfonyloxymethyl)-2,3,8,9-tetrahydro-7H-1,4-dioxino[2,3-e]indol-8-one

Product 1

HCID 158784AplindoreYield 101.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A 25 mL, flask is charged with [(2R)-8-oxo-2,3,8,9-tetrahydro-7H-[1,4]dioxino[2,3-e]indol-2-yl]methyl 4-methylbenzenesulfonate (1.00 g, 2.7 mmol) and DMSO (8.0 mL). Nitrogen gas is bubbled through the solution for 10 min, benzylamine (0.73 mL, 6.7 mmol) is added and nitrogen is bubbled through the mixture for another 15 min. The flask is immersed in an 85° C. oil bath and stirred for 18 h. The solution is cooled, water (24 mL) is added and the resulting solution is extracted with MTBE (3×15 mL). The combined organic extracts are washed successively with water (10 mL), saturated NH4Cl (10 mL) and saturated NaHCO3 (10 mL), and are evaporated to give the crude title compound (0.85 g, 101%) as a red syrup. LCMS (Basic Method): 1.84 min, 311 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 10.4 (br s, 1H), 7.35-7.27 (m, 5H), 6.73 (d, J=8.3 Hz, 1H), 6.36 (d, J=8.3 Hz, 1H), 4.37-4.35 (m, 1H), 4.25 (dd, J=2.2, 11.5 Hz, 1H), 4.03 (dd, J=7.3, 11.5 Hz, 1H), 3.88 (s, 2H), 3.44 (s, 2H), 2.97-2.88 (m, 2H), 8.9 (br s, 1H).

Workup

  1. customNitrogen gas is bubbled through the solution for 10 min
  2. customnitrogen is bubbled through the mixture for another 15 min
  3. customis immersed in an 85° C.
  4. temperatureThe solution is cooled
  5. additionwater (24 mL) is added
  6. extractionthe resulting solution is extracted with MTBE (3×15 mL)
  7. washThe combined organic extracts are washed successively with water (10 mL), saturated NH4Cl (10 mL) and saturated NaHCO3 (10 mL)
  8. customare evaporated

Sources & evidence

ORD record
ord-80c2d9c057c24f19ae38bf78cf6af492
Source dataset
uspto-grants-2013_06
Patent number
US08466296B2

Reaction notes

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