m-Chloroperbenzoic acid → HCID 178465309, compound

HRID 447254Notes

Reaction equation

HRID 447254 reaction equation
[C:1]([N:8]([CH2:37][CH3:38])[C:9]([NH:11][C:12]1[NH:16][C:15]2[C:17]([C@H:32]3[CH2:36][CH2:35][CH2:34][O:33]3)=[C:18]([F:31])[C:19]([C:21]3[CH:22]=[N:23][C:24]([C:27]([OH:30])([CH3:29])[CH3:28])=[N:25][CH:26]=3)=[CH:20][C:14]=2[N:13]=1)=[O:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=NN=N1.CC(N([P:51]([O:60][CH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[O:52]CC1C=CC=CC=1)C(C)C)C.C1C=C(Cl)C=C(C(OO)=[O:76])C=1>C(Cl)Cl>[CH2:61]([O:60][P:51]([OH:52])([O:33][CH2:32][C:17]1[CH:15]=[CH:14][CH:20]=[CH:19][CH:18]=1)=[O:76])[C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=1.[C:1]([N:8]([CH2:37][CH3:38])[C:9]([NH:11][C:12]1[NH:16][C:15]2[C:17]([C@H:32]3[CH2:36][CH2:35][CH2:34][O:33]3)=[C:18]([F:31])[C:19]([C:21]3[CH:22]=[N:23][C:24]([C:27]([OH:30])([CH3:28])[CH3:29])=[N:25][CH:26]=3)=[CH:20][C:14]=2[N:13]=1)=[O:10])([O:3][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:2]

Participants

6

Reactant 4

HCID 70297m-Chloroperbenzoic acidHCID 196621Bis(benzyloxy)(diisopropylamino)phosphineHCID 178418441HCID 178418441, compoundHCID 178465308HCID 178465308, compound

Product 1

HCID 178465309HCID 178465309, compoundYield 128.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To Boc-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 (25) (12.69 g, 23.58 mmol) and tetrazole (3.304 g, 47.16 mmol) under N2 at 23° C. was added DCM (240 mL) followed by N-dibenzyloxyphosphanyl-N-isopropyl-propan-2-amine (9.775 g, 9.509 mL, 28.30 mmol). After 3 hours at 23° C., the reaction was cooled to 0° C. then mCPBA (6.977 g, 28.30 mmol) was added. The resulting solution was stirred for 45 min at 0° C. then for 20 min at 23° C. The reaction mixture was then partitioned between DCM (50 mL) and saturated aqueous sodium bicarbonate (400 mL). The organic layer was separated, then washed successively with aqueous sodium bisulfite (63 g in 350 mL water) and saturated aqueous sodium bicarbonate (400 mL), then dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by MPLC using an ISCO COMBIFLASH brand flash chromatography purification system (330 g silica column) eluting with a 0-100% EtOAc in hexanes linear gradient over 16 column volumes at 200 mL/min. Product containing fractions were evaporated in vacuo to give Boc-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 (26) (11.92 g, 15.11 mmol, 64.09%). ESMS (M+1)=789.2; 1H NMR (300.0 MHz, CDCl3) δ 9.51 (s, 1H), 9.03 (t, J=5.4 Hz, 1H), 8.91 (d, J=1.6 Hz, 2H), 7.73 (d, J=6.5 Hz, 1H), 7.37-7.28 (m, 10H), 5.58 (t, J=7.8 Hz, 1H), 5.17-5.05 (m, 4H), 4.23 (t, J=7.5 Hz, 1H), 4.05 (td, J=7.8, 4.3 Hz, 1H), 3.53-3.44 (m, 2H), 2.39 (dd, J=7.9, 14.5 Hz, 2H), 2.28-2.15 (m, 2H), 1.98 (s, 6H), 1.72 (m, 9H) and 1.31 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. waitfor 20 min at 23° C
  2. customThe reaction mixture was then partitioned between DCM (50 mL) and saturated aqueous sodium bicarbonate (400 mL)
  3. customThe organic layer was separated
  4. washwashed successively with aqueous sodium bisulfite (63 g in 350 mL water) and saturated aqueous sodium bicarbonate (400 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by MPLC
  9. customan ISCO COMBIFLASH brand flash chromatography purification system (330 g silica column)
  10. washeluting with a 0-100% EtOAc in hexanes linear gradient over 16 column volumes at 200 mL/min
  11. additionProduct containing fractions
  12. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-8da7f1999b2042888a57bab83b579336
Source dataset
uspto-grants-2013_07
Patent number
US08481551B2

Reaction notes

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