Bromotrimethylsilane → HCID 178520282, compound

HRID 1525331Notes

Reaction equation

HRID 1525331 reaction equation
[OH:1][C:2]1[C:7]([NH:8][C:9](=[O:25])[CH2:10][C:11]2[CH:12]=[C:13]([P:17](=[O:24])([O:21]CC)[O:18]CC)[CH:14]=[CH:15][CH:16]=2)=[CH:6][N:5]=[C:4]([C:26]2[N:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[OH:1][C:2]1[C:7]([NH:8][C:9](=[O:25])[CH2:10][C:11]2[CH:12]=[C:13]([P:17](=[O:18])([OH:24])[OH:21])[CH:14]=[CH:15][CH:16]=2)=[CH:6][N:5]=[C:4]([C:26]2[N:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[N:3]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 178476960HCID 178476960, compound

Product 1

HCID 178520282HCID 178520282, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

A solution of diethyl 3-(2-(4-hydroxy-2-(pyridazin-3-yl)pyrimidin-5-ylamino)-2-oxoethyl)phenyl-phosphonate (35i, 280 mg, 0.63 mmol) in DCM (20 mL) was added with TMSBr (1.9 g, 12.6 mmol) and stirred at 30° C. for overnight. The reaction mixture was concentrated in vacuum. The residue was added with MeOH (50 mL), stirred for 20 min, and concentrated. The residue was added with water (20 mL) and MeCN (0.5 mL). The solids were filtered to afford the pure product, 35-1, as a white solid (70 mg, 29%). 1H NMR (300 MHz, DMSO) δ 3.9 (s, 2H), 7.39-7.58 (m, 3H), 7.70 (d, J=12.9 Hz, 1H), 7.93 (m, 1H), 8.42 (d, J=8.7 Hz, 1H), 8.86 (m, 1H), 9.40 (d, J=4.2 Hz, 1H), 9.84 (m, 1H), LC-MS (M+H)+ 388.1

Workup

  1. concentrationThe reaction mixture was concentrated in vacuum
  2. additionThe residue was added with MeOH (50 mL)
  3. stirringstirred for 20 min
  4. concentrationconcentrated
  5. additionThe residue was added with water (20 mL) and MeCN (0.5 mL)
  6. filtrationThe solids were filtered
  7. customto afford the pure product, 35-1

Sources & evidence

ORD record
ord-332569ac3585445c95848e7978ccd961
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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