Chloroform methanol → HCID 86724351, compound

HRID 1482697Notes

Reaction equation

HRID 1482697 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:20]1[N:25]=[C:24]([NH:26][C:27]2[CH:28]=[C:29]([NH:33][C:34](=[O:37])[CH:35]=[CH2:36])[CH:30]=[CH:31][CH:32]=2)[C:23]([F:38])=[CH:22][N:21]=1.C(Cl)(Cl)Cl.CO>C(O)CCC>[Si:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:20]2[N:25]=[C:24]([NH:26][C:27]3[CH:28]=[C:29]([NH:33][C:34](=[O:37])[CH:35]=[CH2:36])[CH:30]=[CH:31][CH:32]=3)[C:23]([F:38])=[CH:22][N:21]=2)=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 21584188Chloroform methanolHCID 86724332HCID 86724332, compoundHCID 86724350HCID 86724350, compound

Product 1

HCID 86724351HCID 86724351, compoundYield 11.6%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent2×

Procedure

A solution of 4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)aniline (4.02 g) and N-(3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)acrylamide (4.0 g) in 1-butanol (10 mL) was heated to 135° C. for 3 hr. The reaction was monitored on TLC using CHCl3:methanol (9.5:0.5) as mobile phase. After completion of the reaction, butanol was removed under reduced pressure and water was added. The mixture was extracted with ethyl acetate. Organic layer was dried over sodium sulfate and solvent was removed under reduced pressure. Crude material was purified by Combiflash chromatography eluting with 2.5% methanol in CHCl3 to give 0.828 g of N-(3-((2-((4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)acrylamide. 1H NMR: DMSO-d6 (400 MHz) 0.036 (s, 6H), 0.844 (s, 9H), 3.859-3.895 (d, 4H), 5.737-5.767 (dd, 1H, J=1.6, 8.4), 6.245-6.292 (dd, 1H, J=2, 15.2), 6.437-6.505 (m, 1H), 6.737-6.760 (d, 2H, J=9.2), 7.252-7.293 (t, 1H, J=8), 7.415-7.542 (m, 4H), 7.944-7.956 (d, 1H, J=4.8), 8.065-8.074 (d, 1H, J=3.6), 8.896 (s, 1H), 8.896 (s, 1H), 9.379 (s, 1H), 10.1190 (s, 1H).

Workup

  1. customwas removed under reduced pressure and water
  2. additionwas added
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialOrganic layer was dried over sodium sulfate and solvent
  5. customwas removed under reduced pressure
  6. customCrude material was purified by Combiflash chromatography
  7. washeluting with 2.5% methanol in CHCl3

Sources & evidence

ORD record
ord-255870011bbe4287bf61eee7f8df7e07
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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