Lithium hydroxide, monohydrate → HCID 86724357, compound

HRID 1482705Notes

Reaction equation

HRID 1482705 reaction equation
[C:1]([NH:5][C:6]1[CH:7]=[C:8]([NH:12][C:13]2[C:18]([F:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]3[CH:33]=[CH:32][C:24]([O:25][CH2:26][C:27]([O:29]CC)=[O:28])=[CH:23][CH:22]=3)[N:14]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:4])[CH:2]=[CH2:3].O[Li].O.C(Cl)(Cl)Cl.CO>CO.O>[C:1]([NH:5][C:6]1[CH:7]=[C:8]([NH:12][C:13]2[C:18]([F:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]3[CH:22]=[CH:23][C:24]([O:25][CH2:26][C:27]([OH:29])=[O:28])=[CH:32][CH:33]=3)[N:14]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:4])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 21584188Chloroform methanolHCID 86724356HCID 86724356, compound

Product 1

HCID 86724357HCID 86724357, compoundYield 40.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

A solution of ethyl 2-(4-((4-((3-acrylamidophenyl)amino)-5-fluoropyrimidin-2-yl)amino)phenoxy)acetate (0.300 g) in methanol was cooled to 0° C. and a solution of LiOH.H2O (0.056 g) in water was added. The reaction mixture was stirred at room temperate for 2 hr. The reaction was monitored on TLC using CHCl3:methanol (8:2) as mobile phase. After completion of the reaction, methanol was removed under reduced pressure and water was added. The aqueous layer was washed with ethyl acetate, acidified with acetic acid and the solid precipitate was filtered and washed with water. Solid material was dried under vacuumed at 45° C. to give 0.115 g of 2-(4-((4-((3-acrylamidophenyl)amino)-5-fluoropyrimidin-2-yl)amino)phenoxy)acetic acid. 1H NMR: DMSO-d6 (400 MHz): 4.492 (s, 2H), 5.740-5.767 (d, 1H, J=10.8), 6.238-6.280 (d, 1H, J=16.8), 6.446-6.513 (dd, 1H, J=6.8, 10), 6.717-6.739 (d, 2H, J=8.8), 7.252-7.292 (t, 1H, J=8), 7.377-7.396 (d, 1H, J=7.6), 7.502-7.523 (d, 3H, J=7.6), 7.961 (s, 1H), 8.060-8.068 (d, 1H, J=3.2), 8.988 (s, 1H), 9.386 (s, 1H), 10.191 (s, 1H).

Workup

  1. customwas removed under reduced pressure and water
  2. additionwas added
  3. washThe aqueous layer was washed with ethyl acetate
  4. filtrationthe solid precipitate was filtered
  5. washwashed with water
  6. customSolid material was dried
  7. customunder vacuumed at 45° C.

Sources & evidence

ORD record
ord-05d039e842c6433591dc043d9d0918ac
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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