Water → HCID 463708, compound

HRID 2393283Notes

Reaction equation

HRID 2393283 reaction equation
[F:1][C:2]([F:8])([CH:5]([F:7])[F:6])[CH2:3][OH:4].[H-].[Na+].[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C@@:19]([OH:40])([CH2:34][N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)[C@H:20]([N:22]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][C:27](F)=[CH:28][CH:29]=2)[N:24]=[CH:23]1)[CH3:21].O>CN1C(=O)CCC1.CCOC(C)=O>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C@@:19]([OH:40])([CH2:34][N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)[C@H:20]([N:22]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][C:27]([O:4][CH2:3][C:2]([F:8])([F:1])[CH:5]([F:7])[F:6])=[CH:28][CH:29]=2)[N:24]=[CH:23]1)[CH3:21]

Participants

7

Reactant 4

HCID 962WaterHCID 64412,2,3,3-Tetrafluoro-1-propanolHCID 24758Sodium hydrideHCID 482331HCID 482331, compound

Product 1

HCID 463708HCID 463708, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2,2,3,3-tetrafluoropropanol (381 mg, 2.9 mmol) in anhydrous NMP (10 mL) was treated with NaH (55% in hexane, 126 mg, 2.9 mmol) for 10 min at room temperature. Once H2 ceased to evolve, (1R,2R)-3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4triazol-1-yl)propyl]-7-fluoroquinazolin-4(3H)-one (400 mg, 0.96 mmol, obtained in example 12) was added and the mixture was stirred at 120° C. overnight. Once the reaction was completed, water and EtOAc were added. The aqueous phase was separated and reextracted with further EtOAc. The combined organic extracts were washed with water and brine, dried over anhydrous Na2SO4, filtered, concentrated and purified by flash chromatography to give the title compound as an amorphous white solid (200 mg, 48%): 1H NMR (300 MHz, CDCl3) δ (TMS) 8.56 (s, 1H, N=CH--N), 8.29 (d, J=9.5, 1H, arom), 7.76 (s, 1H, triazole), 7.74 (s, 1H, triazole), 7.48 (dt, Jd =6.5, Jt =8.8, 1H, arom), 7.15 (m, 2H, arom), 6.9-6.7 (m, 2H, arom), 6.08 (tt, J=4.5, J=53, 1H, CHF2), 5.92 (dq, Jd =2, Jq =7.3, 1H, MeCH), 5.51 (d, J=1.5, 1H, OH), 5.16 (d, J=14.3, 1H, CH(H)), 4.49 (tt, J=1.5, J=12, 2H, CH2), 4.01 (d, J=14.3, 1H, CH(H)), 1.29 (d, J=7.3, 3H, CHMe); GC/MS 304 (N-ethylheterocycle group, C13H12F4N2O2), 224 (Tr--CH2COHAr, C10H8F2N3O); [α]D =-16.7° (c 1, CHCl3). Analysis calculated for C23 H19F6N5O3 : C 52.38; H 3.63; N 13.28. Found: C 51.84; H 3.68; N 12.29.

Workup

  1. customThe aqueous phase was separated
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-c32de81cdc0245a08450d0f3c304b6af
Source dataset
uspto-grants-1998_09
Patent number
US05807854

Reaction notes

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