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 587338ノート

反応式

HRID 587338 の反応式
[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

参加物

6

反応物 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

生成物 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 ester収率 32%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-aba469d1b2d04503bbfcea129ac21d75
出典データセット
uspto-grants-2016_01
特許番号
US09226916B2

反応ノート

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