Methanol → HCID 178485570, compound

HRID 2279903Notes

Reaction equation

HRID 2279903 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:37]=[CH:36][C:27]([CH2:28][CH2:29][CH2:30][PH:31](=[O:35])[O:32]CC)=[CH:26][C:25]=3[O:38][CH3:39])[N:14]=2)=[CH:4][CH:3]=1.Br[Si](C)(C)C.CO>N1C=CC=CC=1>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:37]=[CH:36][C:27]([CH2:28][CH2:29][CH2:30][PH:31](=[O:32])[OH:35])=[CH:26][C:25]=3[O:38][CH3:39])[N:14]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 76113BromotrimethylsilaneHCID 178476802HCID 178476802, compound2×

Product 1

HCID 178485570HCID 178485570, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of ethyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)ethylphosphinate (Compound 67C, 1.11 g, 1.76 mmol) in pyridine (15.0 mL) was cooled to 0° C. and then charged with bromotrimethylsilane (1.39 mL, 10.6 mmol). The reaction mixture was slowly warmed to rt with stirring for 72 hours. The reaction mixture was quenched with MeOH (2.3 mL, 57 mmol) and then concentrated under reduced pressure to a yellow oil. The material was dissolved in DCM (10 mL) and washed with 3N HCl (10 mL), was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to a light yellow solid. The acid layer was saturated with solid NaCl and extracted with DCM (10 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to a light yellow solid. Both batches of solid were combined (932.5 mg, 88%). 1H NMR (CDCl3, 400 MHz): δ=8.91 (d, J=8.3 Hz, 1H), 8.34 (s, 1H), 8.10 (q, J=4.6 Hz, 1H), 7.47 (d, J=8.8 Hz, 1H), 6.89 (s, 1H), 6.82 (d, J=8.1 Hz, 1H), 3.87 (s, 3H), 3.00-3.10 (m, 5H), 1.54-1.68 (m, 2H), 1.13 (td, J=7.5, 18.3 Hz, 3H). MS (ESI): m/z 603.42/605.40 [M+H]+. UPLC: tR=1.24 min (UPLC-SQD: analytical—2 min).

Workup

  1. concentrationconcentrated under reduced pressure to a yellow oil
  2. dissolutionThe material was dissolved in DCM (10 mL)
  3. washwashed with 3N HCl (10 mL)
  4. washwas washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a light yellow solid
  8. extractionextracted with DCM (10 mL)
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to a light yellow solid
  12. customtR=1.24 min (UPLC-SQD: analytical—2 min)

Sources & evidence

ORD record
ord-63cdc611383f477684bf8283c71146a6
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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