Methanol → HCID 178485570、化合物

HRID 2279903ノート

反応式

HRID 2279903 の反応式
[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

参加物

5

反応物 3

HCID 887MethanolHCID 76113BromotrimethylsilaneHCID 178476802HCID 178476802、化合物2 回

生成物 1

HCID 178485570HCID 178485570、化合物

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-63cdc611383f477684bf8283c71146a6
出典データセット
uspto-grants-2015_09
特許番号
US09133224B2

反応ノート

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