Methanesulfonyl chloride → HCID 86724354, compound

HRID 1482699Notes

Reaction equation

HRID 1482699 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]2[N:24]=[C:23]([NH:25][C:26]3[CH:27]=[C:28]([NH:32][C:33](=[O:38])[CH:34]([OH:37])[CH2:35][OH:36])[CH:29]=[CH:30][CH:31]=3)[C:22]([F:39])=[CH:21][N:20]=2)=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:40][S:41](Cl)(=[O:43])=[O:42].C(Cl)(Cl)Cl.CO.C([O-])(O)=O.[Na+]>C1COCC1.O>[CH3:40][S:41]([O:36][CH2:35][CH:34]([OH:37])[C:33]([NH:32][C:28]1[CH:29]=[CH:30][CH:31]=[C:26]([NH:25][C:23]2[C:22]([F:39])=[CH:21][N:20]=[C:19]([NH:18][C:15]3[CH:14]=[CH:13][C:12]([O:11][CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])=[CH:17][CH:16]=3)[N:24]=2)[CH:27]=1)=[O:38])(=[O:43])=[O:42]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 21584188Chloroform methanolHCID 86724352HCID 86724352, compound

Product 1

HCID 86724354HCID 86724354, compoundYield 10.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 25 mL 3-neck RBF equipped with a calcium chloride guard tube, N-(3-((2-((4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide (2.0 g), in THF (25 mL), was added TEA (0.724 g). The reaction mixture was cooled to 0° C. and a solution of CH3SO2Cl (0.491 g) in THF was added dropwise. The reaction mixture was stirred at room temperature for 3 hr. The reaction was monitored on TLC using CHCl3:methanol (9:1) as mobile phase. After completion of reaction, water and saturated NaHCO3 solution were added. The mixture was extracted into ethyl acetate. The organic layer was washed dried over sodium sulfate and concentrated under reduced pressure at 40° C. The crude material was purified by Combiflash eluted with 2.2% methanol in CHCl3 to give 0.24 g of 3-((3-((2-((4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate.

Workup

  1. customIn a 25 mL 3-neck RBF equipped with a calcium chloride guard tube
  2. additionwere added
  3. extractionThe mixture was extracted into ethyl acetate
  4. washThe organic layer was washed
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure at 40° C
  7. customThe crude material was purified by Combiflash
  8. washeluted with 2.2% methanol in CHCl3

Sources & evidence

ORD record
ord-4a96a8b40db94a6f8458fced23c8be76
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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