Water → HCID 86724355, compound

HRID 1482701Notes

Reaction equation

HRID 1482701 reaction equation
[Si]([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]([CH:35]4[CH2:37][O:36]4)=[O:34])[CH:29]=[CH:30][CH:31]=3)[C:22]([F:38])=[CH:21][N:20]=2)=[CH:14][CH:13]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(Cl)(Cl)Cl.CO.O>C1COCC1>[F:38][C:22]1[C:23]([NH:25][C:26]2[CH:27]=[C:28]([NH:32][C:33]([CH:35]3[CH2:37][O:36]3)=[O:34])[CH:29]=[CH:30][CH:31]=2)=[N:24][C:19]([NH:18][C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:10][CH2:9][OH:8])=[CH:13][CH:14]=2)=[N:20][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 21584188Chloroform methanolHCID 86724353HCID 86724353, compound

Product 1

HCID 86724355HCID 86724355, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(3-((2-((4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamide (0.160 g) in THF was cooled to 0° C. and TBAF was added. The reaction mixture was stirred at 0° C. for 1 hr. The reaction was monitored on TLC using CHCl3:methanol (9:1) as mobile phase. After completion, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and solvent was removed under reduced pressure. The crude material was purified by Combiflash eluted with 3.1% methanol in CHCl3 to give 0.051 g of N-(3-((5-fluoro-2-((4-(2-hydroxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamide. 1H NMR: DMSO-d6 (400 MHz): 2.676-2.901 (q, 1H), 2.974-3.00 (q, 1H), 3.575-3.674 (m, 2H), 3.901-3.926 (m, 2H), 4.830-4.858 (t, 1H, J=5.6), 6.764-6.786 (d, 1H, J=8.8), 7.256-7.296 (d, 1H, J=8), 7.345-7.366 (d, 1H, J=8.4), 7.514-7.537 (d, 3H, J=9.2), 7.933 (s, 1H), 8.065-8.074 (d, 1H, J=3.6), 8.896 (s, 1H), 9.391 (s, 1H), 10.119 (s, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate and solvent
  3. customwas removed under reduced pressure
  4. customThe crude material was purified by Combiflash
  5. washeluted with 3.1% methanol in CHCl3

Sources & evidence

ORD record
ord-e8c1c3cfb42b4795b9c5240df966c8c0
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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