Sodium hydride → HCID 49779446, compound

HRID 1773277Notes

Reaction equation

HRID 1773277 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:17][CH2:16][CH:7]2[NH:8][C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][C:14]=3[CH:6]2[CH2:5]1.[CH2:18]([C:20]1([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH2:22][O:21]1)[CH3:19]>CN(C=O)C>[CH3:3][N:4]1[CH2:17][CH2:16][C:7]2[N:8]([CH2:22][C:20]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)([OH:21])[CH2:18][CH3:19])[C:9]3[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][C:14]=3[C:6]=2[CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 65684DicarbineHCID 14684538HCID 14684538, compound

Product 1

HCID 49779446HCID 49779446, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A flask was charged with sodium hydride (0.640 g, 50-60%) in dry DMF (10 mL) at 0° C. and to this was added 2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (0.8 g). The mixture was stirred at RT for 30 min and then 4-(2-ethyloxiran-2-yl)pyridine (0.834 g) dissolved in DMF (2 mL) was added, stirred at RT for 12 h. The reaction mixture was diluted with ice-water and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and evaporated. The crude product was triturated with diethyl ether to obtain the desired compound. The racemic compound was further separated into the (R) and (S) enantiomers by use of chiral HPLC. 1HNMR (DMSO, Oxalate salt) d (ppm): 8.45 (d, 2H), 7.42 (d, 2H), 7.30 (d, 1H), 7.10 (s, 1H), 6.82 (d, 1H), 4.30 (d, 1H), 4.18 (d, 1H), 3.60 (s, 2H), 3.50 (m, 2H), 3.38 (m, 1H), 3.0 (m, 2H), 2.90 (s, 3H), 3.32 (s, 3H), 2.10 (m, 1H), 0.6 (t, 3H).

Workup

  1. additionwas added
  2. stirringstirred at RT for 12 h
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe crude product was triturated with diethyl ether

Sources & evidence

ORD record
ord-fbd665ef5aee48449c4c7e5988a433d1
Source dataset
uspto-grants-2016_02
Patent number
US09255094B2

Reaction notes

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