Diisopropylethylamine → rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-[1,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587338노트

반응식

HRID 587338 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.Br[C:35]1[S:36][CH:37]=[N:38][N:39]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:35]4[S:36][CH:37]=[N:38][N:39]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 27951982-Bromo-1,3,4-thiadiazoleHCID 58303080[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

생성물 1

HCID 58303145rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-[1,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester수율 32%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (100 mg, 0.20 mmol) in N-methylpyrrolidinone (1 mL) was added 2-bromo-1,3,4-thiadiazole (50 mg, 0.30 mmol) and N,N-diisopropyl ethyl amine (69 μl, 0.40 mmol). The solution was irradiated in the microwave for 35 min at 150° C. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated and washed with brine (15 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20) afforded the title compound (37 mg, 32%) as an off-white foam. MS m/e: 578.1 [M]+.

후처리

  1. customThe solution was irradiated in the microwave for 35 min at 150° C
  2. washwashed with an aqueous solution of sodium carbonate (1 M, 15 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (15 mL)
  5. extractionthe aqueous layers were extracted with ethyl acetate (20 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20)

출처 및 근거

ORD 기록
ord-aba469d1b2d04503bbfcea129ac21d75
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09226916B2

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