Triethylamine → (5R)-3-{6-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5-ethyl-2,4-imidazolidinedione

HRID 527705노트

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HRID 527705 반응식
[NH2:1][C@H:2]([CH2:24][CH3:25])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[CH:16]=[CH:15][CH:14]=2)=[CH:10][CH:11]=1)=[O:4].C(N(CC)CC)C.Cl[C:34](Cl)([O:36]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>ClCCl>[CH3:23][C:20]1([CH3:22])[CH2:19][C:18]2[C:13]([O:12][C:9]3[N:8]=[CH:7][C:6]([N:5]4[C:3](=[O:4])[C@@H:2]([CH2:24][CH3:25])[NH:1][C:34]4=[O:36])=[CH:11][CH:10]=3)=[CH:14][CH:15]=[CH:16][C:17]=2[O:21]1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 67958761(2R)-2-amino-N-{6-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}butanamide

생성물 1

HCID 57410583(5R)-3-{6-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5-ethyl-2,4-imidazolidinedione

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

((2R)-2-amino-N-{6-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}butanamide) (Intermediate 209, 10 mg, 0.029 mmol) was dissolved in dry dichloromethane (1 ml). The reaction mixture was cooled down in an ice bath. Triethylamine (0.024 ml, 0.176 mmol) was added at 0° C. Then 0.5 ml of a solution of triphosgene in dry dichloromethane (4.78 mg, 0.016 mmol in 0.5 ml) was added dropwise. The reaction mixture was stirred under argon during 20 min at 0° C. A saturated aqueous solution of NaHCO3 was added (3 ml). The aqueous layer was extracted with dichloromethane 4 times (4×4 mL). Combined organic layers were dried over Na2SO4 and evaporated. the residue was purified by flash chromatography (Companion system) on silica gel using a 4 g silica cartridge and cyclohexane/ethyl acetate from 100:0 to 60:40 as eluents affording the title compound (7 mg).

후처리

  1. temperatureThe reaction mixture was cooled down in an ice bath
  2. extractionThe aqueous layer was extracted with dichloromethane 4 times (4×4 mL)
  3. dry with materialCombined organic layers were dried over Na2SO4
  4. customevaporated
  5. customthe residue was purified by flash chromatography (Companion system) on silica gel using a 4 g silica cartridge and cyclohexane/ethyl acetate from 100:0 to 60:40 as eluents

출처 및 근거

ORD 기록
ord-762754c6ee2c44e482ab09fd8975a47a
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

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