4-Methylmorpholine → [1-(4-Chloro-2-methylbenzyl)-2-oxo-2-(4-quinazolin-4-yl-piperazin-1-yl)-ethyl]-carbamic acid tert-butyl ester

HRID 1192366노트

반응식

HRID 1192366 반응식
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[CH3:21])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1.[N:50]1([C:56]2[C:65]3[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=3)[N:59]=[CH:58][N:57]=2)[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[CH3:21])[C:10](=[O:12])[N:53]1[CH2:54][CH2:55][N:50]([C:56]2[C:65]3[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=3)[N:59]=[CH:58][N:57]=2)[CH2:51][CH2:52]1)([CH3:2])([CH3:3])[CH3:4]

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 18585334-Piperazin-1-ylquinazolineHCID 67538859Boc-4-chloro-2-methyl-DL-phenylalanine

생성물 1

HCID 67539682[1-(4-Chloro-2-methylbenzyl)-2-oxo-2-(4-quinazolin-4-yl-piperazin-1-yl)-ethyl]-carbamic acid tert-butyl ester수율 95%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution containing 2-tert-Butoxycarbonylamino-3-(4-chloro-2-methyl-phenyl)-propionic acid (200 mg, 0.64 mmol) in 30 mL of DMF was added HOBT (0.12 g, 0.76 mmol), EDCI (0.15 g, 0.76 mmol) and NMM (0.19 g, 1.9 mmol) under a nitrogen atmosphere. After stirring for 10 minutes, 4-Piperazin-1-yl-quinazoline (200 mg, 0.93 mmol) was added and stirring continued overnight. The reaction was diluted with ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 10% MeOH/DCM gave [1-(4-Chloro-2-methylbenzyl)-2-oxo-2-(4-quinazolin-4-yl-piperazin-1-yl)-ethyl]-carbamic acid tert-butyl ester (0.31 g, 95%.) LCMS (APCI+) m/z 510 [M+H]+; Rt: 2.54 min.

후처리

  1. stirringstirring continued overnight
  2. washwashed with water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationFiltration, removal of solvent and purification of the residue via biotage
  5. washeluting with 10% MeOH/DCM

출처 및 근거

ORD 기록
ord-df2792a664b049c6978870c144394f57
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680114B2

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