4-Methylmorpholine → Pavinetant

HRID 655905ノート

反応式

HRID 655905 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.[C:54]1([C@@H:60]([NH2:63])[CH2:61][CH3:62])[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1>O1CCCC1>[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]([NH:63][C@H:60]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[CH2:61][CH3:62])=[O:18])=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:4])=[O:3]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6993773(1S)-1-phenylpropan-1-amineHCID 578935713-[(Methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acid

生成物 1

HCID 23649245Pavinetant収率 15.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 3-[(methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acid (1c) (342 mg, 1.0 mmol), HOBT hydrate (231 mg, 1.5 mmol), 4-methylmorpholine (276 μL, 1.5 mmol) in tetrahydrofuran (50 ml) was added EDCI (289 mg, 1.5 mmol) at RT under N2. (S)-1-Phenyl propylamine (135 mg, 1.0 mmol) was then added and the reaction mixture stirred at RT for 12 h. All solvent was removed in vacuo and the residue was partitioned between ethyl acetate and 10% aqueous sodium bicarbonate solution, dried over sodium sulfate and then concentrated in vacuo. The residue was purified by chromatography eluting with 15-25% ethyl acetate/hexane to give the title compound (70 mg, 15%) as a solid. 1H NMR (300 MHz, CDCl3) δ 0.94 (t, 3H), 1.97 (m, 2H), 3.44 (s, 3H), 5.17 (q, 1H), 5.47 (m, 2H), 7.32 (d, 2H), 7.34 (d, 2H), 7.39 (m, 1H), 7.78 (m, 2H), 7.84 (m, 2H), 8.08 (m, 1H), 8.30 (m, 2H), 8.42 (m, 2H). MS APCI, m/z=460 (M+1). LCMS: 2.51 min.

後処理

  1. customAll solvent was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate and 10% aqueous sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by chromatography
  6. washeluting with 15-25% ethyl acetate/hexane

出典と根拠

ORDレコード
ord-3be33431aac149cab0f50804043a3fd1
出典データセット
uspto-grants-2011_12
特許番号
US08071621B2

反応ノート

読み込み中…