Sodium hydride → HCID 68816999, compound

HRID 735207Notes

Reaction equation

HRID 735207 reaction equation
I[C:2]1[C:10]2[N:9]([CH3:11])[C@H:8]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=C[C:18]=1[C:23]1[CH:28]=[CH:27][C:26]([SH:29])=[CH:25][CH:24]=1.[H-].[Na+]>[Cu](I)I.CN1CCCN(C)C1=O>[CH3:16][N:14]1[CH2:13][CH2:12][C@@H:8]2[N:9]([CH3:11])[C:10]3[C:2]([S:29][C:26]4[CH:27]=[CH:28][C:23]([CH3:18])=[CH:24][CH:25]=4)=[CH:3][CH:4]=[CH:5][C:6]=3[C@@H:7]2[CH2:15]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 67183685HCID 67183685, compoundHCID 68817017HCID 68817017, compound

Product 1

HCID 68816999HCID 68816999, compound

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
100 °C

Procedure

(4aS,9bR)-6-Iodo-2,5-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (910 mg, 2.7 mmol) was combined with p-tolylthiophenol (426 mg, 3.3 mmol), sodium hydride (132 mg, 3.3 mmol, 60% in oil dispersion), copper iodide (515 mg, 2.7 mmol) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (5 mL) and stirred at 100° C. for 16 hours. The reaction mixture was partitioned between water and CHCl3. The aqueous layer was extracted with CHCl3 (3×20 mL). The combined organics were washed with sat. NaCl (10 mL), water (10 mL), dried (MgSO4) and evaporated. The residue was loaded onto a SCX resin. The resin was washed with 150 mL of MeOH followed by washing with 2.0 M methanolic ammonia. The collected residue was dissolved in CH3CN and 1N HCl/Ether was added until no further precipitation was observed. The solid was filtered and washed with CH3CN affording the title compound (315 mg, 36%) as a white solid. 1H NMR (CD3OD, 300 MHz) δ 7.20 (d, 1H, J=7.7 Hz), 7.14 (d, 1H, J=7.3 Hz), 7.06 (d, 2H, J=8.1 Hz), 6.97 (d, 2H, J=8.4 Hz), 6.82-6.87 (m, 1H), 3.99-4.05 (m, 1H), 3.71-3.80 (m, 1H), 3.15-3.25 (m, 4H), 3.08 (s, 3H), 2.99 (s, 3H), 2.38-2.43 (m, 1H), 2.26 (s, 3H), 1.90-2.03 (m, 1H) ppm.

Workup

  1. customThe reaction mixture was partitioned between water and CHCl3
  2. extractionThe aqueous layer was extracted with CHCl3 (3×20 mL)
  3. washThe combined organics were washed with sat. NaCl (10 mL), water (10 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. washThe resin was washed with 150 mL of MeOH
  7. washby washing with 2.0 M methanolic ammonia
  8. dissolutionThe collected residue was dissolved in CH3CN
  9. addition1N HCl/Ether was added until no further precipitation
  10. filtrationThe solid was filtered
  11. washwashed with CH3CN affording the title compound (315 mg, 36%) as a white solid

Sources & evidence

ORD record
ord-df11fb0ddd0d4aa09a9ea52be3aab1f1
Source dataset
uspto-grants-2009_09
Patent number
US07592454B2

Reaction notes

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