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

HRID 1959990노트

반응식

HRID 1959990 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-7c5cc16528944c00bfadfdbf35f7022a
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410279B2

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