Triphosgene → (5R)-5-methyl-3-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-2,4-imidazolidinedione

HRID 1023604노트

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HRID 1023604 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:14]=[CH:13][C:12]([NH:15][C:16](=[O:20])[C@@H:17]([CH3:19])[NH2:18])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[O:21][CH3:22].Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:19][C@H:17]1[NH:18][C:24](=[O:26])[N:15]([C:12]2[CH:13]=[N:14][C:9]([O:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([O:21][CH3:22])[CH:4]=3)=[CH:10][CH:11]=2)[C:16]1=[O:20]

참가 물질

4

반응물 2

HCID 94429TriphosgeneHCID 67235885HCID 67235885, 화합물2회

생성물 1

HCID 53241719(5R)-5-methyl-3-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-2,4-imidazolidinedione수율 137.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

To a solution of N1-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-D-alaninamide (Intermediate 52, 255 mg) in dry dichloromethane (15 mL), TEA (0.590 mL, 4.23 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (113 mg, 0.381 mmol) in dry dichloromethane (DCM) (5 mL) was slowly added and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with water (10 mL) and extracted with dichloromethane (20 mL). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by silica gel chromatography (Biotage system, 10 g SNAP column) using as eluent a gradient cyclohexane/ethyl acetate from 70/30 to 30/70. This afforded the title compound as a white solid (172 mg, 0.525 mmol).

후처리

  1. customThe reaction was quenched with water (10 mL)
  2. extractionextracted with dichloromethane (20 mL)
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified by silica gel chromatography (Biotage system, 10 g SNAP column)

출처 및 근거

ORD 기록
ord-c6e64f67a41c496b872ce83fee6e3e29
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722695B2

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