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

HRID 1192366ノート

反応式

HRID 1192366 の反応式
[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]

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-df2792a664b049c6978870c144394f57
出典データセット
uspto-grants-2014_03
特許番号
US08680114B2

反応ノート

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