Piperidine → 1-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

HRID 80399

反応式

HRID 80399 の反応式
[NH2:1][C@@H:2]([CH:22]([CH3:24])[CH3:23])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:4].C([N:42]=[C:43]=[S:44])(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2.N1CCCCC1>C(Cl)Cl>[Br:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[NH:11][C:10]([C@@H:6]3[CH2:7][CH2:8][CH2:9][N:5]3[C:3](=[O:4])[C@@H:2]([NH:1][C:43]([NH2:42])=[S:44])[CH:22]([CH3:24])[CH3:23])=[N:14][CH:13]=2)=[CH:20][CH:19]=1

参加物

5

反応物 3

HCID 8082Piperidine2 回HCID 4154759Fmoc isothiocyanateHCID 57610942(S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one

生成物 1

HCID 576109411-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one (1.530 g, 3.91 mmol) in CH2Cl2 (10 mL) was added O-(9H-fluoren-9-yl)methyl carbonisothiocyanatidate (1.100 g, 3.91 mmol) as a solid in one portion. The mixture was allowed to stir at room temperature for 12 h. Piperidine (2 mL) was added to the mixture and it was allowed to stir at room temperature for 1 h. A further portion of piperidine (2 mL) was added and the solution allowed to stir 1 h. The solution was concentrated to dryness and the residue was purified by column chromatography (biotage, eluting with 5:4.5:0.5 hex:EtOAc:MeOH, and then 5% MeOH in EtOAc). The title compound as obtained as a light yellow glass (1.30 g, 74%). 1HNMR (300 MHz, DMSO-d6) δ 11.81 (s, H), 7.65 (d, J=8.8 Hz), 7.63-7.71 (m, overlap with previous peak, 2H total), 7.42-7.56 (m, 2H), 7.10-7.14 (m, 1H), 5.06 (dd, J=7.0, 3.0 Hz, 1H), 4.94 (app t, J=8.0 Hz, 1H), 4.72-4.76 and 4.56-4.62 (m, 1H, rotamers, 1:1 ratio), 3.77-3.90 (m, 1H), 2.07-2.14 (m, 2H), 1.90-1.98 (m, 3H), 0.93 (d, J=7.0 Hz, 3H), 0.84 (d, J=7.0 Hz, 3H). LCMS: Anal. Calcd. for C19H24BrN5OS: 449, 451; found: 450, 452 (M+H)+.

後処理

  1. stirringto stir at room temperature for 1 h
  2. stirringto stir 1 h
  3. concentrationThe solution was concentrated to dryness
  4. customthe residue was purified by column chromatography (biotage
  5. washeluting with 5:4.5:0.5 hex

出典と根拠

ORDレコード
ord-d205494fb6e94a9c8a8e916e1da150f2
出典データセット
uspto-grants-2014_09
特許番号
US08846023B2

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