Tetrahydrofuran → N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

HRID 2274260Notes

Reaction equation

HRID 2274260 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:18]=[C:19](NC(=O)C=C)C=C[CH:22]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C[N+:29]1([O-])[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[C:36](OCC)(=[O:38])C.C1C[O:45]CC1>O.O=[Os](=O)(=O)=O>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[C:34]([NH:29][C:30](=[O:45])[CH:31]([OH:32])[CH2:36][OH:38])[CH:33]=[CH:19][CH:18]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 86724331N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

Product 1

HCID 86724334N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent

Procedure

Into a 25 mL 3-neck RBF equipped with a calcium chloride guard tube, N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide (I-3) (0.100 g), in THF (4 mL), NMO (0.032 g) and OsO4(4% in water) solution were charged at room temperature The reaction mixture was stirred at room temperature for approx. 4 h. The reaction was monitored on TLC using ethyl acetate (100%) as mobile phase. After completion, the reaction mixture was poured in water and extracted into ethyl acetate. Organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure at 40° C. Crude material was purified by preparative HPLC using 0.1% TFA in ACN and 0.1% TFA in water as mobile phase to give 10 mg of N-(3-((5-fluoro-2-((4-hydroxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide. 1H NMR: DMSO-d6 (400 MHz) 3.58-3.61 (m, 2H), 4.045-4.059 (t, 1H, J=4), 4.836-4.851 (d, 1H, J=6), 5.771-5.785 (d, 1H, J=5.6), 6.605-6.627 (d, 2H, J=8.8), 7.201-7.242 (t, 1H, J=8), 7.377-7.442 (m, 3H), 7.541-7.561 (d, 1H, J=8), 7.953 (s, 1H), 8.020-8.029 (d, 1H, J=3.6), 8.827 (s, 1H), 8.931 (s, 1H), 9.300 (s, 1H), 9.520 (s, 1H).

Workup

  1. customInto a 25 mL 3-neck RBF equipped with a calcium chloride guard tube
  2. extractionextracted into ethyl acetate
  3. washOrganic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure at 40° C
  6. customCrude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-82ece546b11a470eac3faae2bb3b7e19
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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