Tetrahydrofuran → HCID 86724333, compound

HRID 2274259Notes

Reaction equation

HRID 2274259 reaction equation
[F:1][C:2]1[C:3]([NH:19][C:20]2[CH:21]=[C:22](NC(=O)C=C)C=C[CH:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][OH:18])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C[N+:32]1([O-])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(Cl)Cl.C[OH:43].C1[CH2:48][O:47]CC1>O.O=[Os](=O)(=O)=O>[F:1][C:2]1[C:3]([NH:19][C:20]2[CH:25]=[C:37]([NH:32][C:33](=[O:43])[CH:34]([OH:35])[CH2:48][OH:47])[CH:36]=[CH:22][CH:21]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][OH:18])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 82029Methyl morpholine oxideHCID 21226129Dichloromethane methanolHCID 75203907HCID 75203907, compound

Product 1

HCID 86724333HCID 86724333, compound

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-(2-hydroxyethoxy)phenyl]amino}pyrimidin-4-yl)amino]phenyl}prop-2-enamide (1-1) (0.120 g), in THF (2 mL), NMO (0.030 g) and OsO4 (0.175 mL 4% in water) solution were charged at room temperature. The reaction mixture was stirred at room temperature for 3 to 4 h. The reaction was monitored on TLC using DCM:methanol (9:1). After completion of the reaction, the reaction mixture was poured in water and extracted into ethyl acetate. The organic layer was washed with sat. bicarbonate, dried over sodium sulfate and concentrated under reduced pressure at 40° C. The compound was purified by reverse phase Combiflash chromatography to give 25 mg of N-(3-((5-fluoro-2-((4-(2-hydroxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide. M+1=443.9. 1H NMR (DMSO-d6, 400 MHz): 3.603 (s, 2H), 3.660 (s, 2H), 3.906-3.930 (t, 2H, J=4.8), 4.062 (s, 1H), 4.846 (s, 2H), 5.791 (s, 1H), 6.782-6.804 (d, 2H, J=8.8), 7.233-7.274 (t, 1H, J=8.4), 7.425-7.445 (d, 1H, J=8), 7.537-7.515 (d, 3H, J=8.8), 7.972 (s, 1H), 8.053-8.062 (d, 1H, J=3.6), 8.983 (s, 1H), 9.345 (s, 1H), 9.557 (s, 1H).

Workup

  1. customInto a 25 mL 3-neck RBF equipped with a calcium chloride guard tube
  2. customAfter completion of the reaction
  3. extractionextracted into ethyl acetate
  4. washThe organic layer was washed with sat. bicarbonate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure at 40° C
  7. customThe compound was purified by reverse phase Combiflash chromatography

Sources & evidence

ORD record
ord-5e9f786767aa4ddea2a9a3420133f1a1
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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