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

HRID 603459Notes

Reaction equation

HRID 603459 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[H-].[Na+].Br[CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[C@H:21]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:20][CH2:19]2.[NH4+].[Cl-]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[C@H:21]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:20][CH2:19]3)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2313102-Amino-5-bromopyrimidineHCID 16110497ethyl[(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300487ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-2-aminopyrimidine (2.35 g, 13.5 mmol) in DMF (50 mL) was added NaH (539 mg, 13.5 mmol of a 60% dispersion in mineral oil) [H2 evolution]. Then, ethyl [(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 45, 2.3 g, 6.74 mmol) was added over 5 min, and the reaction mixture was stirred at rt for 4 h, after which NH4Cl (10% aqueous solution) was added, and the mixture was concentrated under reduced pressure. The residue was taken up in EtOAc and 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 (400 MHz, CDCl3) δ 1.27 (t, 3H), 1.70-1.81 (m, 1H), 2.02-2.12 (m, 2H), 2.34-2.43 (m, 1H), 2.41 (dd, 1H), 2.73 (dd, 1H), 2.77-2.94 (m, 2H), 3.48-3.56 (m, 1H), 3.58 (q, 2H), 4.03 (t, 2H), 4.18 (q, 2H), 5.95 (b t, 1H), 6.69 (dd, 1H), 6.75 (d, 1H), 7.04 (d, 1H), 8.22 (s, 2H).

Workup

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

Sources & evidence

ORD record
ord-011efced57d247c9a8f413a31ac63df2
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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