m-Chloroperbenzoic acid → HCID 178465481, compound

HRID 447257Notes

Reaction equation

HRID 447257 reaction equation
[C:1]([N:8]([C:21]1[NH:25][C:24]2[C:26]([C@H:41]3[CH2:45][CH2:44][CH2:43][O:42]3)=[C:27]([F:40])[C:28]([C:30]3[CH:31]=[N:32][C:33]([C:36]([OH:39])([CH3:38])[CH3:37])=[N:34][CH:35]=3)=[CH:29][C:23]=2[N:22]=1)[C:9](=[O:20])[N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=NN=N1.CC(N([P:58]([O:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[O:59]CC1C=CC=CC=1)C(C)C)C.C1C=C(Cl)C=C(C(OO)=[O:83])C=1>C(Cl)Cl>[CH2:68]([O:67][P:58]([OH:59])([O:42][CH2:41][C:26]1[CH:24]=[CH:23][CH:29]=[CH:28][CH:27]=1)=[O:83])[C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=1.[C:1]([N:8]([C:21]1[NH:25][C:24]2[C:26]([C@H:41]3[CH2:45][CH2:44][CH2:43][O:42]3)=[C:27]([F:40])[C:28]([C:30]3[CH:31]=[N:32][C:33]([C:36]([OH:39])([CH3:38])[CH3:37])=[N:34][CH:35]=3)=[CH:29][C:23]=2[N:22]=1)[C:9](=[O:20])[N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH3:12])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 178418441HCID 178418441, compoundHCID 178465480HCID 178465480, compound

Product 1

HCID 178465481HCID 178465481, compoundYield 129%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To diBoc-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-[(2R)-tetrahydrofuran-2-yl]-1H-benzimidazol-2-yl]urea (28) (1.13 g, 1.797 mmol) and tetrazole (251.8 mg, 3.594 mmol) at 23° C. under N2 was added DCM (30 mL) followed by N-dibenzyloxyphosphanyl-N-isopropyl-propan-2-amine (744.7 mg, 724.4 μA, 2.156 mmol). After stirring for 18 h, the reaction was cooled to 0° C. then treated with mCPBA (531.5 mg, 2.156 mmol). The reaction was stirred for 15 min at 0° C., then for 30 min at 23° C. The resulting solution was then partitioned between EtOAc and saturated aqueous sodium bicarbonate (300 mL each), the organic layer separated, then washed with 10% aqueous sodium bisulfite, saturated aqueous sodium bicarbonate and brine (300 mL each), then dried over magnesium sulfate filtered and concentrated. The residue was purified by MPLC using an ISCO COMBIFLASH brand flash chromatography purification system (80 g silica column) eluting with a 0-80% EtOAc in hexanes linear gradient over 20 column volumes at 60 mL/min flow rate. Desired product fractions were combined and evaporated to give diBoc-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-[(2R)-tetrahydrofuran-2-yl]-1H-benzimidazol-2-yl]urea dibenzyl phosphate (29) (1.03 g, 1.159 mmol, 64.50%) as a clear, glassy oil. ESMS (M+1)=889.5; 1H NMR (300.0 MHz, CDCl3) δ 8.93 (d, J=1.5 Hz, 2H), 8.31 (s, 1H), 8.04 (d, J=6.4 Hz, 1H), 7.36-7.26 (m, 10H), 5.83-5.70 (m, 1H), 5.16-5.05 (m, 4H), 4.24-4.18 (m, 1H), 4.03-3.97 (m, 1H), 3.42-3.36 (m, 2H), 2.43-2.05 (m, 4H), 1.98 (s, 6H), 1.64 (s, 9H), 1.40 (s, 9H) and 1.26 (t, J7.2 Hz, 3H) ppm.

Workup

  1. stirringThe reaction was stirred for 15 min at 0° C.
  2. waitfor 30 min at 23° C
  3. customThe resulting solution was then partitioned between EtOAc and saturated aqueous sodium bicarbonate (300 mL each)
  4. customthe organic layer separated
  5. washwashed with 10% aqueous sodium bisulfite, saturated aqueous sodium bicarbonate and brine (300 mL each)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by MPLC
  10. customan ISCO COMBIFLASH brand flash chromatography purification system (80 g silica column)
  11. washeluting with a 0-80% EtOAc in hexanes linear gradient over 20 column volumes at 60 mL/min flow rate
  12. customevaporated

Sources & evidence

ORD record
ord-44bed02e0e5a4f3782efa3a80320966f
Source dataset
uspto-grants-2013_07
Patent number
US08481551B2

Reaction notes

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