Bromotrimethylsilane → HCID 178491167, compound

HRID 1525316Notes

Reaction equation

HRID 1525316 reaction equation
[OH:1][C:2]1[C:7]([C:8]([NH:10][CH:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:12]2[CH:26]=[CH:25][C:15]([CH2:16][P:17](=[O:24])([O:21]CC)[O:18]CC)=[CH:14][CH:13]=2)=[O:9])=[CH:6][N:5]=[C:4]([C:35]2[N:36]=[N:37][CH:38]=[CH:39][CH:40]=2)[N:3]=1.C[Si](Br)(C)C>C(Cl)Cl>[OH:1][C:2]1[C:7]([C:8]([NH:10][CH:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:12]2[CH:13]=[CH:14][C:15]([CH2:16][P:17](=[O:18])([OH:21])[OH:24])=[CH:25][CH:26]=2)=[O:9])=[CH:6][N:5]=[C:4]([C:35]2[N:36]=[N:37][CH:38]=[CH:39][CH:40]=2)[N:3]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 178476847HCID 178476847, compound

Product 1

HCID 178491167HCID 178491167, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

diethyl 4-((4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamido)(4-methoxyphenyl)methyl)benzylphosphonate (32-g, 450 mg, 0.8 mmol) was dissolved in DCM (10 ml), TMSBr (1.8 g, 12 mmol) was then added, the reaction mixture was stirred for 14 h at ambient temperature, monitored by TLC. The resulting mixture was concentrated under reduce pressure, the residue was dissolved in CH3CN (5 ml), diluted with water (10 ml), stirred for 10 min, filtered, washed with water, purified by pre-HPLC, the pure product 32-1 was obtained as a white solid (104 mg, 26% yield). 1H NMR (300 MHz, CD3OD) δ2.97-3.04 (d, J=21.6 Hz 2H) 3.67 (s, 1H) 6.17 (s, 1H), 6.78-6.81 (m, 2H) 7.12-7.20 (m, 6H), 7.80-7.90 (m, 1H), 8.49-8.58 (m, 1H), 8.75 (s, 1H), 9.28 (m, 1H). LC-MS 508 [MH]+.

Workup

  1. concentrationThe resulting mixture was concentrated
  2. dissolutionthe residue was dissolved in CH3CN (5 ml)
  3. additiondiluted with water (10 ml)
  4. stirringstirred for 10 min
  5. filtrationfiltered
  6. washwashed with water
  7. custompurified by pre-HPLC, the pure product 32-1

Sources & evidence

ORD record
ord-3c5f8acbb7914aaf8fafcf568550a45e
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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