3-Furanol, tetrahydro- → HCID 178521597, compound

HRID 1672449Notes

Reaction equation

HRID 1672449 reaction equation
[O:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1.[H-].[Na+].F[C:10]1[CH:19]=[C:18]2[C:13]([CH:14]=[N:15][C:16]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]3)=[N:17]2)=[CH:12][CH:11]=1>C1COCC1>[O:1]1[CH2:5][CH2:4][CH:3]([O:6][C:10]2[CH:19]=[C:18]3[C:13]([CH:14]=[N:15][C:16]([NH:20][C@H:21]4[CH2:22][CH2:23][C@H:24]([OH:27])[CH2:25][CH2:26]4)=[N:17]3)=[CH:12][CH:11]=2)[CH2:2]1

Participants

5

Reactant 3

HCID 99603-Furanol, tetrahydro-HCID 24758Sodium hydrideHCID 178521596HCID 178521596, compound

Product 1

HCID 178521597HCID 178521597, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tetrahydrofuran-3-ol (337 mg, 3.83 mmol) in THF (5 mL) was added NaH (153 mg, 60% disp. in oil, 3.83 mmol) and the mix stirred at r.t. for 20 min., forming a pale suspension. To this was added trans-4-[(7-fluoroquinazolin-2-yl)amino]cyclohexanol (100 mg, 0.383 mmol) and a yellow suspension formed almost immediately. The suspension was stirred at r.t. for 30 min then heated to 45° C. for 1 hour, then heated to 65° C. for 30 min then cooled to R.T. overnight. The liquors were concentrated and diluted with water (10 mL) and EtOAc (25 mL) and shaken vigorously. The aq. was removed and the organics washed with water (10 mL), brine (10 mL), dried over MgSO4, filtered and stripped to an oil. Purified by prep TLC eluting with EtOAc to yield the title compound as a white foam, 36 mg, 29%. 1H NMR (400 MHz, DICHLOROMETHANE-D2) δ ppm 8.75 (1H, s) 7.53 (1H, d, J=8.84 Hz) 6.62-6.88 (2H, m) 5.18 (1H, d, J=7.83 Hz) 5.05 (1H, s) 3.81-4.08 (5H, m) 3.54-3.79 (2H, m) 2.22-2.43 (1H, m) 2.08-2.21 (3H, m) 1.91-2.07 (2H, m) 1.36-1.51 (4H, m) 1.19-1.38 (4H, m); MS (API+) for C18H23N3O3 m/z 330.2 (M+H)+.

Workup

  1. customforming a pale suspension
  2. customa yellow suspension formed almost immediately
  3. stirringThe suspension was stirred at r.t. for 30 min
  4. temperaturethen heated to 45° C. for 1 hour
  5. temperatureheated to 65° C. for 30 min
  6. temperaturethen cooled to R.T. overnight
  7. concentrationThe liquors were concentrated
  8. additiondiluted with water (10 mL) and EtOAc (25 mL)
  9. stirringshaken vigorously
  10. customThe aq. was removed
  11. washthe organics washed with water (10 mL), brine (10 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customPurified by prep TLC
  15. washeluting with EtOAc

Sources & evidence

ORD record
ord-5a31192a2f9c4c3e954766b47c80579a
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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