Nitrogen → 3-((3-((5-Fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate

HRID 2274257Notes

Reaction equation

HRID 2274257 reaction equation
N#N.[F:3][C:4]1[C:5]([NH:22][C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:35])[CH:31]([OH:34])[CH2:32][OH:33])[CH:26]=[CH:27][CH:28]=2)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:13][CH:12]=2)=[N:8][CH:9]=1.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C1COCC1.C(OCC)(=O)C>[CH3:36][S:37]([O:33][CH2:32][CH:31]([OH:34])[C:30]([NH:29][C:25]1[CH:26]=[CH:27][CH:28]=[C:23]([NH:22][C:5]2[C:4]([F:3])=[CH:9][N:8]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:13][CH:12]=3)[N:6]=2)[CH:24]=1)=[O:35])(=[O:39])=[O:38]

Participants

6

Reactant 3

HCID 947NitrogenHCID 31297Methanesulfonyl chlorideHCID 72165218N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

Product 1

HCID 902338843-((3-((5-Fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonateYield 32%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 25 mL 3-neck RBF equipped with N2-bubbler and thermo-pocket, N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide (I-4) (0.08 g) was dissolved in THF (5 mL), TEA (0.0212 g) was added at room temperature. The reaction mixture was cooled to 0° C. Methane sulphonyl chloride (0.021 g) was slowly added at 0° C. The reaction mixture was stirred at room temperature for 1 h. The reaction was monitored on TLC by using ethyl acetate (100%) as mobile phase. (Only 50% of the reaction was complete on TLC). The reaction was diluted with ethyl acetate (20 mL), washed with saturated NaHCO3 (25 mL). The organic layer was separated and dried over sodium sulfate. Ethyl acetate was removed under reduced pressure at 40° C. Crude material was purified by Combiflash chromatography eluted with 7% ethyl acetate in hexane. The solvent was removed under vacuum to give 0.03 g of 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate.

Workup

  1. washwashed with saturated NaHCO3 (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. customEthyl acetate was removed under reduced pressure at 40° C
  5. customCrude material was purified by Combiflash chromatography
  6. washeluted with 7% ethyl acetate in hexane
  7. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-87c4cc0ae4ff45259d51c4fba90c9186
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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