(S)-3-Amino-1-methyl-piperidine → 1-(3-Fluorophenyl)-4-ureido-1H-pyrrole-3-carboxylic acid ((S)-1-methyl-piperidin-3-yl)-amide

HRID 1959990ノート

反応式

HRID 1959990 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH2:8])[CH2:3]1.C[Al](C)C.C([O:15][C:16]([C:18]1[C:22]([NH:23][C:24]([NH2:26])=[O:25])=[CH:21][N:20]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=2)[CH:19]=1)=O)C>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:16]([C:18]2[C:22]([NH:23][C:24]([NH2:26])=[O:25])=[CH:21][N:20]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=3)[CH:19]=2)=[O:15])[CH2:3]1

参加物

5

反応物 3

HCID 7446915(S)-3-Amino-1-methyl-piperidineHCID 16682925TrimethylaluminumHCID 670305681-(3-fluorophenyl)-4-ureido-1H-pyrrole-3-carboxylic acid ethyl ester

生成物 1

HCID 672033191-(3-Fluorophenyl)-4-ureido-1H-pyrrole-3-carboxylic acid ((S)-1-methyl-piperidin-3-yl)-amide収率 17%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of (S)-1-methyl-piperidin-3-yl amine (120 mg, 1.05 mmol) in THF (8.0 mL), under nitrogen, was added 2N trimethylaluminium in hexanes (1.0 mL, 2.0 mmol), and the reaction mixture was allowed to stir at room temperature for 1.5 hours. After this time, a THF (5.0 mL) solution of 1-(3-fluorophenyl)-4-ureido-1H-pyrrole-3-carboxylic acid ethyl ester (291 mg, 1.0 mmol), was added and the reaction mixture was heated at 65-70° C. for a period of 18 hours. After this time, the reaction mixture was allowed to cool to room temperature and was then quenched by addition of a saturated solution of Rochelle's salt. After 0.5 hours, the mixture was extracted with DCM (3×10 mL) and EtOAc (1×10 mL). The combined organic layer was dried (MgSO4) and concentrated in vacuo. The resultant residue was then purified by flash chromatography (silica, 5 g column, Isolute, 0-20% MeOH in DCM) to afford the title compound (60 mg, 0.17 mmol, 17%). LCMS (method A), RT=5.13 min, M+H+=360; 1H NMR (DMSO-D6, 400 MHz): 8.97 (s, 1H), 8.05 (d, J=2.6 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.56 (d, J=2.6 Hz, 1H), 7.55-7.48 (m, 1H), 7.39 (dt, J=10.6, 2.3 Hz, 1H), 7.36-7.33 (m, 1H), 7.12 (td, J=8.5, 2.4 Hz, 1H), 6.29 (s, 2H), 3.95-3.88 (m, 1H), 2.85-2.77 (m, 1H), 2.65-2.57 (m, 1H), 2.18 (s, 3H), 1.92-1.73 (m, 3H), 1.74-1.67 (m, 1H), 1.58-1.46 (m, 1H), 1.33-1.19 (m, 1H).

後処理

  1. temperaturethe reaction mixture was heated at 65-70° C. for a period of 18 hours
  2. temperatureto cool to room temperature
  3. customwas then quenched by addition of a saturated solution of Rochelle's salt
  4. waitAfter 0.5 hours
  5. extractionthe mixture was extracted with DCM (3×10 mL) and EtOAc (1×10 mL)
  6. dry with materialThe combined organic layer was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was then purified by flash chromatography (silica, 5 g column, Isolute, 0-20% MeOH in DCM)

出典と根拠

ORDレコード
ord-7c5cc16528944c00bfadfdbf35f7022a
出典データセット
uspto-grants-2013_04
特許番号
US08410279B2

反応ノート

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