Trimethylsilyl iodide → HCID 72700425, compound

HRID 591389Notes

Reaction equation

HRID 591389 reaction equation
C([O:3][P:4]([N:9]([S:16]([C:19]1[CH:20]=[N:21][CH:22]=[C:23]([C:25]2[N:34]=[C:33]([NH:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][C:31]=3[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[N:26]=2)[CH:24]=1)(=[O:18])=[O:17])[P:10](=[O:15])([OH:14])[O:11]CC)([O:6]CC)=[O:5])C.I[Si](C)(C)C>C(Cl)Cl>[C:43]1([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:32]=2[C:33]([NH:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)=[N:34][C:25]([C:23]2[CH:24]=[C:19]([S:16]([N:9]([P:4]([OH:5])([OH:6])=[O:3])[P:10](=[O:11])([OH:15])[OH:14])(=[O:18])=[O:17])[CH:20]=[N:21][CH:22]=2)=[N:26]3)[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 90019290HCID 90019290, compound

Product 1

HCID 72700425HCID 72700425, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of ethyl hydrogen diethoxyphosphoryl((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)phosphoramidate (9) (0.040 g, 0.056 mmol) in DCM (5 mL) was added iodotrimethylsilane (0.067 g, 0.34 mmol) dropwise, under a nitrogen atmosphere at 0° C. The mixture was stirred for 2 h at 0° C. and the solvent was removed under reduced pressure. The residue was cooled to 0° C. and treated with a mixture of acetone (10 mL) and H2O (0.20 mL). After stirring at 0° C. for 1 h, the mixture was stirred at room temperature overnight. The resulting suspension was filtered and the solid was washed with acetone (20 mL), dried and purified by preparative HPLC to afford ((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)(phosphono)phosphoramidic acid (10) (0.025 g, 0.040 mmol, 71% yield) as a white solid. Preparative HPLC Conditions: Column: KROMASIL® C-4 (250×21.2) mm, 5 μm, Mobile Phase A: 10 mM ammonium acetate in water, Mobile Phase B: acetonitrile, Gradient: 20 to 40% B over 7 min, 100% B for 12.5 min., Flow Rate: 17 mL/min., Retention time: 9 min.; 1H NMR (400 MHz, DMSO-d6) δ (ppm) 4.78 (d, J=3.76 Hz, 2H), 6.96 (br. s., 1H), 7.23 (dd, J=6.53, 5.27 Hz, 1H), 7.31 (dd, J=7.03, 1.25 Hz, 1H), 7.41 (d, J=7.78 Hz, 1H), 7.51-7.61 (m, 5H), 7.73 (td, J=7.65, 1.76 Hz, 1H), 7.80-7.88 (m, 1H), 7.96 (dd, J=8.41, 1.13 Hz, 1H), 8.23 (d, J=4.27 Hz, 1H), 9.11 (d, J=2.01 Hz, 1H) 9.17 (t, J=2.01 Hz, 1H), 9.67 (d, J=2.01 Hz, 1H); 31P (162.0 MHz, DMSO-d6) δ (ppm) −8.820, −8.917, −15.535, −15.629; LCMS Method I: retention time 1.56 min, [M−1]=627. HPLC Method H: Purity 95.0%, retention time 5.27 min.

Workup

  1. customat 0° C
  2. customthe solvent was removed under reduced pressure
  3. temperatureThe residue was cooled to 0° C.
  4. additiontreated with a mixture of acetone (10 mL) and H2O (0.20 mL)
  5. stirringAfter stirring at 0° C. for 1 h
  6. stirringthe mixture was stirred at room temperature overnight
  7. filtrationThe resulting suspension was filtered
  8. washthe solid was washed with acetone (20 mL)
  9. customdried
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-b7ce8dac830440c099c23b03c7c4d8eb
Source dataset
uspto-grants-2016_01
Patent number
US09238666B2

Reaction notes

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