Trifluoroacetic acid → HCID 178493878, compound

HRID 339769Notes

Reaction equation

HRID 339769 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:7]([CH2:23][CH2:24][N:25]=3)[C:8]([NH:14][C:15]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[O:16])=[N:9][C:10]=2[C:11]=1[O:12][CH3:13].C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:44][C@@H:45]1[O:47][CH2:46]1)(=O)=O>CN(C=O)C>[CH3:13][O:12][C:11]1[C:10]2[N:9]=[C:8]([NH:14][C:15](=[O:16])[C:17]3[CH:22]=[CH:21][CH:20]=[N:19][CH:18]=3)[N:7]3[CH2:23][CH2:24][N:25]=[C:6]3[C:5]=2[CH:4]=[CH:3][C:2]=1[O:1][CH2:44][C@H:45]1[CH2:46][O:47]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 12461091HCID 12461091, compound2×HCID 178493831HCID 178493831, compound2×

Product 1

HCID 178493878HCID 178493878, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-{8-hydroxy-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}pyridine-3-carboxamide (Intermediate I, Step 2 (used as bis-TFA salt), 1.50 g, 2.65 mmol) and caesium carbonate (4.32 g, 13.3 mmol, 5.0 equiv.) in DMF (37 mL) was stirred at room temperature for 1 h, then was treated with (R)-glycidyl methanesulfonate (Intermediate F, Step 1, 21.2 mL, 0.25 M in DMF, 5.31 mmol, 2.0 equiv.). The resulting mixture was stirred at room temperature for 16 h at 60° C., then was cooled to room temperature and concentrated under reduced pressure. The resulting residue was seperated between water (50 mL) and a 4:1 CH2Cl2/isopropanol solution (50 mL). The organic phase was washed with a concentrated sodium bicarbonate solution, dried (anh. sodium sulfate), and concentrated under reduced pressure. The resulting material was triturated with EtOH and dried under reduced pressure to give N-{7-methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}nicotinamide (0.72 g, 69%): HPLC ret. time 0.94 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 2.75 (dd, J=2.5, 5.1 Hz, 1H), 2.88 (app t, J=4.7, 1H), 3-42-3.47 (m, 1H), 4.01 (s, 3H), 4.14 (dd, J=6.6, 11.6 Hz, 1H), 4.20-4.29 (m, 3H), 4.52-4.59 (m, 2H), 4.68 (dd, J=2.3, 11.6 Hz, 1H), 7.47 (d, J=9.4 Hz, 1H), 7.92 (dd, J=5.6, 7.8 Hz, 1H), 8.03 (d, J=9.1 Hz, 1H), 8.90 (br d, J=7.8 Hz, 1H), 8.97 (dd, J=1.5, 5.6 Hz, 1H), 9.49 (d, J=1.5 Hz, 1H); mass spectrum m/z 394 ((M+1)+, 11%).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 16 h at 60° C.
  2. temperaturewas cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was seperated between water (50 mL)
  5. washThe organic phase was washed with a concentrated sodium bicarbonate solution
  6. dry with materialdried (anh. sodium sulfate)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting material was triturated with EtOH
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-0782bd9d5dfd4e86a5bd400f8190cdf8
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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