Triethylamine → (R)-1-[8-((R)-1-phenyl-propylcarbamoyI)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbonyl]-pyrrolidine-2-carboxylic acid methyl ester

HRID 926396노트

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HRID 926396 반응식
[C:1]1([C@H:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([C:22](O)=[O:23])[N:16]3[CH2:21][CH2:20][O:19][CH2:18][C:17]=23)=[O:12])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:48][O:49][C:50]([C@H:52]1[CH2:56][CH2:55][CH2:54][NH:53]1)=[O:51].C(N(CC)CC)C>CN(C)C=O.ClCCl>[CH3:48][O:49][C:50]([C@H:52]1[CH2:56][CH2:55][CH2:54][N:53]1[C:22]([C:15]1[N:16]2[C:17]([CH2:18][O:19][CH2:20][CH2:21]2)=[C:13]([C:11](=[O:12])[NH:10][C@@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][CH3:9])[CH:14]=1)=[O:23])=[O:51]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44629857Methyl D-prolinate hydrochlorideHCID 89726203HCID 89726203, 화합물

생성물 1

HCID 89726390(R)-1-[8-((R)-1-phenyl-propylcarbamoyI)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbonyl]-pyrrolidine-2-carboxylic acid methyl ester수율 21%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
25 °C

실험 절차

To a solution of 8-((R)-1-phenyl-propylcarbamoyI)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carboxylic acid (Comp. No. 11a) (200 mg, 0.61 mmol) in dimethylformamide (2 ml) was added 1-hydroxybenzotriazole (91 mg, 0.670 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (128 mg, 0.670 mmol). The mixture was stirred for 45 min at 25° C., then (R)-pyrrolidine-2-carboxylic acid methyl ester hydrochloride (111 mg, 0.670 mmol) and triethylamine (123 mg, 1.218 mmol) were added and the mixture was stirred at 25° C. overnight. Excess dichloromethane was added and the mixture was washed consecutively with water, aqueous sodium hydrogencarbonate and brine. The organic layer was evaporated to dryness. The crude product was purified by flash chromatography (silica gel, elution with heptane/ethyl acetate) to give 55 mg (21%) of (R)-1-[8-((R)-1-phenyl-propylcarbamoyI)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbonyl]-pyrrolidine-2-carboxylic acid methyl ester). LC/MS (method 4): Rt=1.21 min; m/z=440.29 (M+H+).

후처리

  1. stirringthe mixture was stirred at 25° C. overnight
  2. washthe mixture was washed consecutively with water, aqueous sodium hydrogencarbonate and brine
  3. customThe organic layer was evaporated to dryness
  4. customThe crude product was purified by flash chromatography (silica gel, elution with heptane/ethyl acetate)

출처 및 근거

ORD 기록
ord-1e207a771c8a48c1b6524f1f03b54527
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09284333B2

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