Sodium hydride → HCID 69890625, compound

HRID 2119495Notes

Reaction equation

HRID 2119495 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=3)[CH:9]2[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:38][C:39]([NH2:41])=[O:40]>C1COCC1.CN(C=O)C>[C:39]([CH2:38][NH:41][C:39](=[O:40])[CH2:38][O:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)=[CH:22][CH:21]=1)[N:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:17][CH2:16]2)(=[O:40])[NH2:41]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 696322-BromoacetamideHCID 54107592HCID 54107592, compound

Product 1

HCID 69890625HCID 69890625, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-fluorophenyl)-1-{4-[(2-piperidyl)ethoxy]benzyl}-1,2,3,4-tetrahydroisoquinolin-6-ol (0.100 g, 0.2 mmol) in THF (1 ml) and DMF (5 drops) on ice was added sodium hydride (0.024 g, 0.6 mmol). To the flask was added bromoacetamide (0.083 g, 0.6 mmol). While warming to room temperature the reaction was allowed to sit for 6 hours. The reaction was quenched with an aqueous solution of sodium bicarbonate and extracted with dichloromethane. The organic layer was dried over MgSO4, filtered and concentrated. The product was purified by semipreparative HPLC (C-18 column, 10-100% acetonitrile/water with 0.1% trifluoroacetic acid) to yield the title compound (0.008 g, 7.0% yield):1H NMR (CDCl3) 6.6-7.3 (m, 11H), 6.0 (broad s, 2H), 5.55 (broad s, 1H), 4.7 (t, 1H), 4.5 (s, 2H), 4.1 (m, 4H), 3.5 (m, 2H), 3.05 (m, 1H), 2.9 (m, 4H), 2.65 (m, 1H), 2.55 (m, 4H), 1.65 (m, 4H), 1.5 (m, 2H); ES−MS (m/z) 575 [M+H]+.

Workup

  1. customThe reaction was quenched with an aqueous solution of sodium bicarbonate
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by semipreparative HPLC (C-18 column, 10-100% acetonitrile/water with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-a96d16f893f5405fb7e0e8f986731218
Source dataset
uspto-grants-2004_02
Patent number
US06686351B2

Reaction notes

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