Pyridine → tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamate

HRID 735530노트

반응식

HRID 735530 반응식
C(Cl)(=O)[C:2](Cl)=[O:3].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH2:18][CH3:19])C(O)=O)=[CH:10][CH:9]=1.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=1)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:18][CH2:19][C:2]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=2)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:3])=[CH:12][CH:13]=1

참가 물질

8

반응물 4

HCID 1049PyridineHCID 574722-(4-Bromophenyl)butanoic acidHCID 65578Oxalyl chlorideHCID 57956368tert-Butyl 5-amino-2-(ethylthio)benzyl(methyl)carbamate

생성물 1

HCID 57956370tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamate수율 88%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

Oxalyl chloride (0.180 mL, 2.06 mmol) was added dropwise to a suspension of 4-bromophenylbutanoic acid (0.250 g, 1.03 mmol) in DCM (3 mL) containing DMF (1 drop) at rt. After 4 h, the reaction mixture was concentrated in vacuo and coevaporated with toluene. The residue was dissolved in DCM (2 mL) and added dropwise to a solution of 17A (0.300 g, 1.01 mmol), DMAP (0.025 g, 0.2 mmol)and pyridine (1.0 mL, 12.3 mmol) in DCM (2 mL) at rt. The reaction mixture was stirred overnight at rt. The reaction mixture was concentrated in vacuo and the residue was triturated with water and then purified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes) to give 17B (0.46 g, 88%) as a clear oil that solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.03 Hz, 3 H) 1.33-1.58 (m, 9 H) 1.96-2.04 (m, 2 H) 2.33 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.74-2.93 (m, 3 H) 4.56 (br. s., 2 H) 6.96-7.02 (m, 0.5 H) 7.05 (d, J=8.35 Hz, 2 H) 7.13 (br. s., 0.4 H) 7.28-7.36 (m, 0.8 H) 7.38 (d, J=8.35 Hz, 2 H) 7.60-7.72 (m, 0.4 H) 7.81-7.98 (m, 0.9 H) 8.33 (br. s., 1 H).

후처리

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was triturated with water
  5. custompurified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-299951a814644dfe8887de927b87117a
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07592331B2

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