Methanol → HCID 178485570, 화합물

HRID 2279903노트

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HRID 2279903 반응식
[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

참가 물질

5

반응물 3

HCID 887MethanolHCID 76113BromotrimethylsilaneHCID 178476802HCID 178476802, 화합물2회

생성물 1

HCID 178485570HCID 178485570, 화합물

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-63cdc611383f477684bf8283c71146a6
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133224B2

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