Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amine → Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amine

HRID 459955Notes

Reaction equation

HRID 459955 reaction equation
[CH:1]1([NH:4][C:5]2[C:10]([CH:11]=[N:12][C:13]3[C:18]([F:19])=[C:17]([O:20][CH3:21])[CH:16]=[C:15]([O:22][CH3:23])[C:14]=3[F:24])=[CH:9][N:8]=[C:7]([S:25][CH3:26])[N:6]=2)[CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH:1]1([NH:4][C:5]2[C:10]([CH2:11][NH:12][C:13]3[C:18]([F:19])=[C:17]([O:20][CH3:21])[CH:16]=[C:15]([O:22][CH3:23])[C:14]=3[F:24])=[CH:9][N:8]=[C:7]([S:25][CH3:26])[N:6]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 18444840Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amineHCID 21226445Aluminium lithium hydride

Product 1

HCID 18444839Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of in 8.61 g (22.6 mmol) of cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amine in 400 mL of dry THF was cooled in an ice/water bath. To the cooled solution was added dropwise equivalent (22.6 mL, 22.6 mmol) of a 1 M LAH solution in THF. The reaction was stirred cold for 2 hours and then quenched by sequential addition of 0.4 mL water, followed by 1.6 mL of 15% NaOH solution, and finally 0.88 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. Stirring the residue with diethyl ether and concentrating the suspension in vacuo gave 8.38 g (97%) of the title compound as a solid: mp 48° C.–50° C. MS (APCI) (m+1)/z 383.4 Analysis calculated for C17H20F2N4SO2: C, 53.39; H, 5.27; N, 14.65. Found: C, 53.44; H, 5.29; N, 14.31.

Workup

  1. customquenched by sequential addition of 0.4 mL water
  2. filtrationThe reaction was filtered through Celite
  3. washthe filter pad was washed well with THF
  4. concentrationThe THF filtrate was concentrated in vacuo
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with a saturated solution of NaCl
  7. concentrationconcentrated in vacuo
  8. stirringStirring the residue with diethyl ether
  9. concentrationconcentrating the suspension in vacuo

Sources & evidence

ORD record
ord-b185df528a5746fe9661f8f55ece2151
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Reaction notes

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