Sodium hydride → 4-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-6-chloro-2-methylpyrimidine

HRID 2175423노트

반응식

HRID 2175423 반응식
[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][OH:17])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:20][C:21]1[CH:26]=[C:25](Cl)[N:24]=[C:23]([CH3:28])[N:22]=1>C1COCC1>[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][O:17][C:25]1[CH:26]=[C:21]([Cl:20])[N:22]=[C:23]([CH3:28])[N:24]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 2349974,6-Dichloro-2-methylpyrimidineHCID 71271332(2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methanol

생성물 1

HCID 867295764-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-6-chloro-2-methylpyrimidine수율 56%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of (2-tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)-methanol (12-5) (130 mg, 0.55 mmol) in THF, sodium hydride (28 mg, 0.69 mmol) was added at 0° C. and it was allowed to stir for 30 min whereupon a solution of 4,6-dichloro-2-methylpyrimidine (113 mg, 0.69 mmol) in THF was added. The solution was heated to reflux overnight. After cooling, it was quenched with water, extracted with EtOAc, dried over sodium sulfate, concentrated under reduced pressure and purified by Pre-TLC (PE/EA=1:1) to afford the product as a white solid (111 mg, 56%). 1H NMR (500 MHz, CDCl3) δ 8.35 (s, 1H), 7.41 (d, J=6.6 Hz, 1H), 7.04 (d, J=8.1 Hz, 1H), 6.59 (s, 1H), 4.49-4.40 (m, 2H), 3.62 (dd, J=6.9, 3.6 Hz, 1H), 2.60 (s, 3H), 2.30 (s, 3H), 2.27 (m, 1H), 2.04 (dd, J=6.7, 3.7 Hz, 1H), 1.08 (s, 9H); LRMS (ES) calculated M+H for C19H25ClN3O2: 362.8. Found: 362.1.

후처리

  1. additionwas added
  2. temperatureThe solution was heated
  3. temperatureto reflux overnight
  4. temperatureAfter cooling
  5. customit was quenched with water
  6. extractionextracted with EtOAc
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. custompurified by Pre-TLC (PE/EA=1:1)

출처 및 근거

ORD 기록
ord-d7599e6788af4b8198ccacbe2aeddd6e
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062059B2

반응 노트

불러오는 중…