4-Methylmorpholine → N-[(1R,2S)-2-hydroxy-1-phenylpropyl]-3-[(methylsulfonyl)amino]-2-phenylquinolin-4-carboxamide

HRID 1822069ノート

反応式

HRID 1822069 の反応式
[CH3:1][S:2]([NH:5][C:6]1[C:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:8][C:9]2[C:14]([C:15]=1[C:16]([OH:18])=O)=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:4])=[O:3].C1C=C2N=NN(O)C2=CC=1.O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.[NH2:55][C@H:56]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[C@@H:57]([OH:59])[CH3:58]>C(Cl)Cl>[OH:59][C@@H:57]([CH3:58])[C@H:56]([NH:55][C:16]([C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:6]=1[NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[O:18])[C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1

参加物

7

反応物 5

HCID 79724-Methylmorpholine2 回HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 578935713-[(Methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acidHCID 68704476(1R,2S)-1-amino-1-phenylpropan-2-ol hydrochloride

生成物 1

HCID 23649332N-[(1R,2S)-2-hydroxy-1-phenylpropyl]-3-[(methylsulfonyl)amino]-2-phenylquinolin-4-carboxamide収率 48%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 3-methanesulfonylamino-2-phenyl-4-carboxylic acid (1c) (250 mg, 0.73 mmol), HOBt hydrate (148 mg, 1.1 mmol), 4-methylmorpholine (160 μL, 1.46 mmol) in methylene chloride (15 mL) was added EDCI (210 mg, 1.1 mmol) at RT under N2. A mixture of (1R,2S)-1-amino-1-phenylpropan-2-ol hydrochloride and 4-methylmorpholine (193 μL, 1.75 mmol), in methylene chloride (5 mL) was added and the reaction mixture was stirred at RT for 16 h. Solution is partitioned against water and twice extracted with methylene chloride. The combined organic extracts are washed with brine, dried over magnesium sulfate and then concentrated in vacuo with added silica. The compound is subsequently eluted off the silica and chromatographed, eluting with 15-30% ethyl acetate/dichloromethane to give the title compound (167 mg, 48%). 1H NMR (500.333 MHz, CDCl3) δ 1.10 (d, J=6.6 Hz, 3H), 2.23 (s, 3H), 2.69 (d′, J=6.7 Hz, 1H), 4.44-4.47 (m, 1H), 5.35 (dd, J=8.4, 3.3 Hz, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.39 (dd, J=6.9, 6.9 Hz, 2H), 7.44 (d, J=7.5 Hz, 2H), 7.47-7.55 (m, 4H), 7.71-7.78 (m, 4H), 8.16 (d, J=8.4 Hz, 1H) MS APCI, m/z=476.1 (M+1). LCMS: 1.86 min.

後処理

  1. customSolution is partitioned against water
  2. extractiontwice extracted with methylene chloride
  3. washThe combined organic extracts are washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo with added silica
  6. washThe compound is subsequently eluted off the silica
  7. customchromatographed
  8. washeluting with 15-30% ethyl acetate/dichloromethane

出典と根拠

ORDレコード
ord-5d7afe61a8f64f59944da933b1aad476
出典データセット
uspto-grants-2009_10
特許番号
US07608628B2

反応ノート

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