Dimethylformamide → ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235928Notes

Reaction equation

HRID 2235928 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[N:6][CH:7]=1.[H-].[Na+].[NH4+].[Cl-].[CH3:32]N(C=O)C>>[Br:1][C:2]1[CH:7]=[N:6][C:5]([N:8]([CH3:32])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[N:4][CH:3]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59300487ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300480ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 21%

Procedure

To a solution of ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}2,3-dihydro-1H-inden-1-yl)acetate (Example 281, 500 mg, 1.15 mmol) in DMF (10 mL) was added NaH [H2 evolution], followed by Mel (180 mg, 1.27 mmol) added over 5 min. The reaction mixture was stirred at rt for 4 h, NH4Cl (10% aqueous solution) was added, after which the mixture was concentrated under reduced pressure. The residue was taken up in EtOAc, then washed with water and brine successively. The organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide the product (600 mg, 21%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.29 (t, 3H), 1.71-1.81 (m, 1H), 2.05-2.13 (m, 2H), 2.34-2.45 (m, 2H), 2.73 (dd, 1H), 2.73-2.94 (m, 2H), 3.14 (s, 3H), 3.49-3.56 (m, 1H), 3.77 (t, 2H), 3.97 (t, 2H), 4.18 (q, 2H), 6.74 (dd, 1H), 6.75 (d, 1H), 7.05 (d, 1H), 8.24 (s, 2H).

Workup

  1. additionadded over 5 min
  2. concentrationafter which the mixture was concentrated under reduced pressure
  3. washwashed with water and brine successively
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-6eb45af4366a48938f3548f63b96be6b
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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