Sodium hydride → ethyl((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)(propyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603489Notes

Reaction equation

HRID 603489 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([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)[C:5]([CH3:28])=[CH:4][N:3]=1.[H-].[Na+].I[CH2:32][CH2:33][CH3:34]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH2:32][CH2:33][CH3:34])[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)[C:5]([CH3:28])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 336431-IodopropaneHCID 59300503ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300511ethyl((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)(propyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 361.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 408, 800 mg, 0.25 mmol) in DMF (20 mL) was added portion wise NaH (118 mg, 2.97 mmol, 60% dispersion in mineral oil) [H2 evolution]. The heterogeneous mixture was stirred for 30 min, then iodopropane (0.39 mL, 3.96 mmol) was added. After 18 h of stirring at rt, the excess NaH was quenched by the slow addition of brine (40 mL) [H2 evolution]. The product was then extracted with Et2O. The combined organic layers were dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (4:1 hexanes/EtOAc) to yield the product (403 mg, 46%). 1H NMR (400 MHz, CDCl3) δ 0.93 (t, 3H), 1.30 (t, 3H), 1.65 (t, 2H), 1.74-1.79 (m, 1H), 2.06-2.11 (m, 2H) 2.27 (s, 3H), 2.37-2.45 (m, 2H), 2.70-2.74 (dd, 1H), 2.84-2.91 (m, 2H), 3.45-3.55 (m, 3H), 3.73 (t, 2H), 3.97 (t, 2H), 4.16 (q, 2H), 6.68 (d, 1H), 6.6.74 (s, 1H), 7.05 (d, 1H), 7.79 (s, 1H).

Workup

  1. stirringAfter 18 h of stirring at rt
  2. customthe excess NaH was quenched by the slow addition of brine (40 mL) [H2 evolution]
  3. extractionThe product was then extracted with Et2O
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-35c228cc614a4329b901e9cbb4ce871f
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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