Diisopropylethylamine → HCID 58777580, compound

HRID 1435313Notes

Reaction equation

HRID 1435313 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([F:16])=[C:14]([F:17])[CH:13]=[C:12]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C:11]=2[O:26][CH3:27])=[O:9])=[CH:6][N:5]=[C:4](Cl)[N:3]=1.FC(F)(F)C(O)=O.[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][CH:43]([NH2:46])[CH2:42][CH2:41]1)(=[O:39])=[O:38].C(N(C(C)C)CC)(C)C>C(O)C>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([F:16])=[C:14]([F:17])[CH:13]=[C:12]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C:11]=2[O:26][CH3:27])=[O:9])=[CH:6][N:5]=[C:4]([NH:46][CH:43]2[CH2:44][CH2:45][N:40]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:41][CH2:42]2)[N:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11975076[1-(Methylsulfonyl)piperidin-4-yl]amine trifluoroacetateHCID 21070551(4-Amino-2-chloro-pyrimidin-5-yl)-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone

Product 1

HCID 58777580HCID 58777580, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (4-amino-2-chloro-pyrimidin-5-yl)-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone (860 mg, 2.0 mmol, Example 269) in ethanol (12 mL) was added 1-methanesulfonyl-piperidin-4-ylamine trifluoroacetate salt (613.8 mg, 2.1 mmol, Example 162) and diisopropylethylamine (1.2 mL, 6.889 mmol). The mixture was heated at reflux for 4 hours and then concentrated to dryness. The residue was dissolved in ethyl acetate (20 mL). The solution was washed with brine (1×10 mL) and dried over anhydrous magnesium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with 45-60% ethyl acetate in hexanes) yielded [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-[3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-methanone as white glass (684 mg, 60%). LR-MS (M+) 572.1.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hours
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
  5. washThe solution was washed with brine (1×10 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe solids were filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customPurification of the crude residue
  10. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with 45-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-325da11b5f584361b07a6efa29265c72
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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