Cesium carbonate → HCID 178493879, compound

HRID 339766Notes

Reaction equation

HRID 339766 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:15][C:16]1[N:25]2[CH2:26][CH2:27][N:28]=[C:24]2[C:23]2[CH:22]=[CH:21][C:20]([OH:29])=[C:19]([O:30][CH3:31])[C:18]=2[N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:43][C@@H:44]1[O:46][CH2:45]1)(=O)=O>CN(C=O)C>[CH3:31][O:30][C:19]1[C:18]2[N:17]=[C:16]([NH2:15])[N:25]3[CH2:26][CH2:27][N:28]=[C:24]3[C:23]=2[CH:22]=[CH:21][C:20]=1[O:29][CH2:43][C@H:44]1[CH2:45][O:46]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 12461091HCID 12461091, compound2×HCID 178493836HCID 178493836, compound2×

Product 1

HCID 178493879HCID 178493879, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-ol bis(trifluoroacetate) (Intermediate E, 0.30 g, 0.65 mmol) in DMF (8 mL) was added caesium carbonate to generate a white suspension. The suspension was stirred at room temperature for 1.5 hr, then (R)-glycidyl methanesulfonate (Intermediate F, Step 1, 3.9 mL of 0.34 M solution in DMF, 1.30 mmol, 2.0 equiv.) was added, and the resulting solution was stirred at 60° C. for 20 h. The resulting suspension was concentrated under reduced pressure and the residue was treated separated between a saturated sodium bicarbonate solution (30 mL) and a 4:1 CH2Cl2/isopropanol solution (30 mL). The aqueous phase was extracted with a 4:1 CH2Cl2/isopropanol solution (30 mL). The combined organic phases were dried (anh. sodium sulfate) and concentrated under reduced pressure. The residue was purified using MPLC (Isolute Flash NH2 reverse phase column; 100% CH2Cl2 for 5 min., gradient to 95% CH2Cl2: 5% MeOH over 15 minutes; gradient to 90% CH2Cl2: 10% MeOH over 15 min.; gradient to 80% CH2Cl2: 20% MeOH over 15 min.; and gradient to 75% CH2Cl2: 25% MeOH over 15 min.) to give 7-methoxy-8-[(2R)-oxiran-2-ylmethoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-amine (0.080 g, 43%): 1H NMR (DMSO-d6+1 drop TFA-d) δ 2.71 (dd, J=2.5, 4.8 Hz, 1H), 2.85, (t, J=4.6 Hz, 1H), 3.34-3.40 (br m, 1H), 3.75 (s, 3H), 3.82 (s, 3H), 4.30 (dd, J=6.6, 11.4 Hz, 1H), 4.10 (br t, J=9.7 Hz, 2H), 4.31 (br t, J=9.7 Hz, 2H), 4.54 (dd, J=2.3, 11.6 Hz, 1H), 7.26 (d, J=9.4 Hz, 1H), 7.84 (d, J=9.1 Hz, 1H).

Workup

  1. stirringthe resulting solution was stirred at 60° C. for 20 h
  2. concentrationThe resulting suspension was concentrated under reduced pressure
  3. additionthe residue was treated
  4. customseparated between a saturated sodium bicarbonate solution (30 mL)
  5. extractionThe aqueous phase was extracted with a 4:1 CH2Cl2/isopropanol solution (30 mL)
  6. dry with materialThe combined organic phases were dried (anh. sodium sulfate)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified
  9. wait100% CH2Cl2 for 5 min.
  10. waitgradient to 95% CH2Cl2: 5% MeOH over 15 minutes
  11. waitgradient to 90% CH2Cl2: 10% MeOH over 15 min.
  12. waitgradient to 80% CH2Cl2: 20% MeOH over 15 min.

Sources & evidence

ORD record
ord-2839eb387d304cce90cba49650a03bf7
Source dataset
uspto-grants-2014_11
Patent number
US08895549B2

Reaction notes

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