4-Methylmorpholine → Pavinetant

HRID 655905노트

반응식

HRID 655905 반응식
[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]

참가 물질

7

반응물 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

생성물 1

HCID 23649245Pavinetant수율 15.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3be33431aac149cab0f50804043a3fd1
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071621B2

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