Bromotrimethylsilane → HCID 10004368, compound

HRID 853709Notes

Reaction equation

HRID 853709 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][NH:11][C:12]([C:14]1[C:15]2[CH:16]=[CH:17][CH:18]=[N:19][C:20]=2[C:21]([O:36]C(C2C=CC=CC=2)C2C=CC=CC=2)=[C:22]2[C:26](=[O:27])[N:25]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:24][C:23]=12)=[O:13])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>ClCCl>[F:35][C:32]1[CH:31]=[CH:30][C:29]([CH2:28][N:25]2[C:26](=[O:27])[C:22]3[C:23](=[C:14]([C:12]([NH:11][CH2:10][CH2:9][P:4](=[O:3])([OH:5])[OH:8])=[O:13])[C:15]4[CH:16]=[CH:17][CH:18]=[N:19][C:20]=4[C:21]=3[OH:36])[CH2:24]2)=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 58652679HCID 58652679, compound

Product 1

HCID 10004368HCID 10004368, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (2-{[9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo [3,4-g]quinoline-5-carbonyl]-amino}-ethyl)-phosphonic acid diethyl ester 214 (16 mg, 0.023 mmol) dissolved in dichloromethane (0.30 ml) was added trimethylsilylbromide (TMS-Br, 39 mg, 0.25 mmol). After 4 hours of stirring at room temperature, more trimethylsilylbromide (24 mg, 0.16 mmol) was added and the reaction mixture stirred for another 2 hours. The reaction mixture was cooled to 0° C., quenched with methanol (1.0 ml), and concentrated in vacuo. It was then triturated three times (3/1—hexane/ether) and the remaining residue in the flask and filter was dissolved in methanol, combined, and concentrated in vacuo. The residue was dissolved in dimethysulfoxide (0.40 ml), filtered through a glass plug, and purified by reverse-phase preparatory HPLC to provide (2-{[7-(4-fluoro-benzyl)-9-hydroxy-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinoline-5-carbonyl]-amino}-ethyl)-phosphonic acid 314 (7 mg, 0.012 mmol, 52%). 1H NMR (CD3OD) δ 8.96 (d, 1H), 8.77 (d, 1H), 7.78 (m, 1H), 7.42 (m, 2H), 7.10 (t, 2H), 4.80 (s, 2H), 4.63 (s, 2H), 3.72 (m, 2H), 2.16 (m, 2H). 31P δ 25.0. 19F δ−78.0, −116.0. MS: 460.1 (M+1).

Workup

  1. stirringthe reaction mixture stirred for another 2 hours
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with methanol (1.0 ml)
  4. concentrationconcentrated in vacuo
  5. customIt was then triturated three times (3/1—hexane/ether)
  6. filtrationthe remaining residue in the flask and filter
  7. dissolutionwas dissolved in methanol
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in dimethysulfoxide (0.40 ml)
  10. filtrationfiltered through a glass plug
  11. custompurified by reverse-phase preparatory HPLC

Sources & evidence

ORD record
ord-0b1b995a3a3843b2963d4840a2a23944
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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