Sodium hydride → HCID 25100942, compound

HRID 1691593Notes

Reaction equation

HRID 1691593 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]([N:12]3[CH2:18][C:17]4([CH3:20])[CH2:19][CH:13]3[CH2:14][C:15]([CH3:22])([CH3:21])[CH2:16]4)=[O:11])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].Br[CH:26]([CH3:32])[C:27]([O:29][CH2:30][CH3:31])=[O:28]>CN(C=O)C>[CH2:30]([O:29][C:27](=[O:28])[CH2:26][CH2:32][N:1]1[C:9]2[C:4](=[C:5]([C:10]([N:12]3[CH2:18][C:17]4([CH3:20])[CH2:19][CH:13]3[CH2:14][C:15]([CH3:22])([CH3:21])[CH2:16]4)=[O:11])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[CH3:31]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79040Ethyl 2-bromopropionateHCID 11437926HCID 11437926, compound

Product 1

HCID 25100942HCID 25100942, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (1H-indol-4-yl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone (82 mg, 0.27 mmol) in dry DMF (2 mL) at room temperature under an inert atmosphere of nitrogen was added sodium hydride (17 mg, 0.69 mmol, 60% dispersion in oil), and after stirring for 30 min ethyl bromopropionate (100 mg, 0.55 mmol) was added, and the reaction mixture was stirred for 72 h at 60° C. The reaction was quenched by the addition of water (20 mL) followed by extraction with DCM (3×50 mL). The combined organic phases were dried (MgSO4), filtered, and evaporated in vacuo. The resulting solid was purified by preparative HPLC, dried in vacuo at 50° C. affording 29 mg (27%) of the title compound as a solid. MS-ESI m/z 397; 1H NMR (400 MHz, DMSO) δ 0.88-1.08 (m, 6H), 1.14-1.22 (m, 7H), 1.28-1.29 (m) and 1.58-1.67 (m, 1H), 1.37-1.43 (m, 3H), 1.77-1.81 (m, 1H), 2.32-2.36 (m) and 3.10-3.20 (m, 1H), 2.81 (t, 2H), 3.35 (dd) and 3.75 (dd, 1H), 4.02-4.04 (m) and 4.68-4.70 (m, 1H), 4.11 (q, 2H), 4.46 (t, 2H), 6.44-6.50 (m, 1H), 7.10-7.13 (m, 1H), 7.17-7.26 (m, 2H), 7.38 (d, 1H).

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of water (20 mL)
  3. extractionfollowed by extraction with DCM (3×50 mL)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting solid was purified by preparative HPLC
  8. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-27e0df6f21c1427a96360178afdf30f3
Source dataset
uspto-grants-2012_04
Patent number
US08153798B2

Reaction notes

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