Cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-amine → Cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-amine

HRID 459957Notes

Reaction equation

HRID 459957 reaction equation
[CH:1]1([NH:6][C:7]2[C:12]([CH:13]=[N:14][C:15]3[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH2:23][CH3:24])[C:16]=3[F:25])=[CH:11][N:10]=[C:9]([S:26][CH3:27])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:1]1([NH:6][C:7]2[C:12]([CH2:13][NH:14][C:15]3[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH2:23][CH3:24])[C:16]=3[F:25])=[CH:11][N:10]=[C:9]([S:26][CH3:27])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 18444838Cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-amineHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 18444837Cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-amineYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

A solution of 8.00 g (20.4 mmol) cyclopentyl-{5-[(3-ethoxy-2,6-difluoro-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl }-amine prepared above, in 200 mL dry THF, was cooled in an ice / water bath. To the cooled solution was added dropwise 1 equivalent (20.4 m, 20.4 mmol) of a 1 M LAH solution in THF. The reaction was stirred cold for 4.5 hours and then warmed to 50° C. for 3.5 hours. The reaction was cooled to room temperature, treated with another 0.5 equivalent (11.0 mL, 11.0 mmol) of 1 M LAH solution in THF, and stirred at room temperature overnight. The reaction was quenched by sequential addition of 1.3 mL water, followed by 5.2 mL of 15% NaOH solution, and finally 2.9 mL of water. The reaction was filtered through Celite and the filter pad was washed well with THF. The THF filtrate was concentrated in vacuo. The residue was dissolved in dichloromethane, washed with a saturated solution of NaCl, and concentrated in vacuo to give 8.03 g (100%) of the title compound as a waxy solid: MS (APCI) (m+1)/z 395.1. Analysis calculated for C19H24F2N4SO: C, 57.85; H, 6.13; N, 14.20. Found: C, 57.92; H, 6.19; N, 14.01.

Workup

  1. temperaturewas cooled in an ice / water bath
  2. temperatureThe reaction was cooled to room temperature
  3. stirringstirred at room temperature overnight
  4. customThe reaction was quenched by sequential addition of 1.3 mL water
  5. filtrationThe reaction was filtered through Celite
  6. washthe filter pad was washed well with THF
  7. concentrationThe THF filtrate was concentrated in vacuo
  8. dissolutionThe residue was dissolved in dichloromethane
  9. washwashed with a saturated solution of NaCl
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a9b05c9425f42c6898f81e4b69a6d1d
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Reaction notes

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