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

HRID 1482673Notes

Reaction equation

HRID 1482673 reaction equation
[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23](NC(=O)C=C)C=C[CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C[N+:33]1([O-])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.[C:40](OCC)(=[O:42])C.[OH2:46]>C1COCC1.O=[Os](=O)(=O)=O>[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:26]=[C:38]([NH:33][C:34](=[O:46])[CH:35]([OH:36])[CH2:40][OH:42])[CH:37]=[CH:23][CH:22]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 59174488Spebrutinib

Product 1

HCID 72165218N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a 25 mL 3-neck RBF equipped with a calcium chloride guard tube N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide (0.275 g) in THF (8 mL), NMO (0.07 g) and OsO4 (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 ethyl acetate (100%) as mobile phase. After completion, the reaction mixture was poured into water and extracted into ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure at 40° C. Crude material was purified by Combiflash chromatography. Product was eluted with 90% ethyl acetate in hexane to give 0.08 g of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide. M+H=457.8 1H NMR: DMSO-d6 (400 MHz): 3.28 (s, 3H), 3.60 (m, 4H), 4.04 (m, 3H), 4.82 (t, 1H, J=5.6), 5.78 (d, 1H, J=5.6), 6.79 (d, 2H, J=8.8), 7.26 (d, 1H, J=8), 7.43 (d, 1H, J=8), 7.52 (d, 3H, J=9.2), 7.97 (s, 1H), 8.05 (d, 1H, J=3.6), 8.98 (s, 1H), 9.34 (s, 1H), 9.55 (s, 1H).

Workup

  1. additionwere charged at room temperature
  2. extractionextracted into ethyl acetate
  3. washThe organic 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 Combiflash chromatography
  7. washProduct was eluted with 90% ethyl acetate in hexane

Sources & evidence

ORD record
ord-597ba733debb4441bcfa11bca54e1041
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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