Trimethylsilyl iodide → HCID 178523841, compound

HRID 1497335Notes

Reaction equation

HRID 1497335 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]1[OH:21])=[O:13])[CH:8]=[C:7]2[CH2:22][C:23]1[CH:24]=[N:25][C:26]([O:29]C)=[CH:27][CH:28]=1.I[Si](C)(C)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][O:18][CH2:17][C@@H:16]1[OH:21])=[O:13])[CH:8]=[C:7]2[CH2:22][C:23]1[CH:24]=[N:25][C:26]([OH:29])=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodide2×HCID 53307810HCID 53307810, compound

Product 1

HCID 178523841HCID 178523841, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 19 (31.2 mg, 0.076 mmol) in CH2Cl2 (506 μl) at 0° C. was added iodotrimethylsilane (20.6 μl, 0.152 mmol). The mixture was stirred at room temperature for overnight. Second portion of TMSI was added and the reaction was heated to 50° C. for 2 h. The reaction mixture was quenched w/H2O, extracted w/EtOAc. The combined organic layers were dried (Na2SO4), filtered, cone. The residue was purified by reverse phase HPLC (C-18 column, 3-70% MeCN in H2O with both containing 0.05% TFA) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=6.8 Hz, 1H), 8.16 (s, 1H), 7.75 (dd, J=2.4, 9.2 Hz, 1H), 7.83 (d, J=9.2 Hz, 1H), 7.63 (dt, J=4.8, 8.0 Hz, 1H), 7.50 (dd, J=8.0, 10.0 Hz, 1H), 7.45 (s, 1H), 6.92 (d, J=8.4 Hz, 1H), 4.41 (s, 2H), 4.13 (dd, J=4.8, 11.2 Hz, 1H), 4.07-4.03 (m, 1H), 3.76 (dt, J=4.8, 9.6 Hz, 1H), 3.52 (dt, J=2.4, 11.6 Hz, 1H), 3.28 (dd, J=10.0, 11.2 Hz, 1H), 2.15-2.10 (m, 1H), 1.95-1.85 (m, 1H). HRMS (ES) [M+1]+ calcd for C22H21FN3O4: 398.1517, Found: 398.1511.

Workup

  1. temperaturethe reaction was heated to 50° C. for 2 h
  2. customThe reaction mixture was quenched w/H2O
  3. extractionextracted w/EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. customThe residue was purified by reverse phase HPLC (C-18 column, 3-70% MeCN in H2O with both containing 0.05% TFA)

Sources & evidence

ORD record
ord-61e3778672844ec8a862866d0d24416b
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

Loading…