Ethanol → 6-({[1-((3R)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)-1-methylethyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one

HRID 639112ノート

反応式

HRID 639112 の反応式
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][C@@H:16]([C:19]([NH2:22])([CH3:21])[CH3:20])[CH2:15]1)=[N:9][C:8]([O:23][CH3:24])=[CH:7][CH:6]=2.CCO.[O:28]=[C:29]1[CH2:34][S:33][C:32]2[CH:35]=[CH:36][C:37]([CH:39]=O)=[N:38][C:31]=2[NH:30]1>C(Cl)Cl>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][C@@H:16]([C:19]([NH:22][CH2:39][C:37]3[CH:36]=[CH:35][C:32]4[S:33][CH2:34][C:29](=[O:28])[NH:30][C:31]=4[N:38]=3)([CH3:21])[CH3:20])[CH2:15]1)=[N:9][C:8]([O:23][CH3:24])=[CH:7][CH:6]=2

参加物

5

反応物 3

HCID 702EthanolHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 59026154HCID 59026154、化合物

生成物 1

HCID 116848996-({[1-((3R)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)-1-methylethyl]amino}methyl)-2H-pyrido[3,2-b][1,4]thiazin-3(4H)-one収率 37%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of the hydrochloride salt of 2-((3R)-1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]ethyl}-3-pyrrolidinyl)-2-propanamine (100 mg, 0.25 mmol) in DCM:EtOH (6 mL, 1:1) were added NaHCO (210 mg, 2.5 mmol) followed by 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (47 mg, 0.25 mmol). After 12 h at 25° C., NaBH (10 mg, 0.28 mmol) was added. After 1 h, the reaction was concentrated and the residue was partitioned between DCM and water. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried over MgSO, concentrated and purified via column chromatography (silica, 0-1% MeOH in DCM (1% NH OH)) yielding the title compound (47 mg, 37%) as an off-white solid: LC/MS (ES) m/e 512 (M+H)+; H NMR (CDCl, 400 Hz) δ 8.59 (s, 1H), 8.17 (d, J=9.1 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.05 (d, J=9.0 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 4.07 (s, 3H), 3.76 (s, 2H), 3.39-3.43 (m, 4H), 2.76-2.96 (m, 4H), 2.55-2.64 (m, 2H), 2.39-2.44 (m, 1H), 1.85-1.88 (m, 1H), 1.72-1.78 (m, 1H), 1.09 (s, 3H), 1.08 (s, 3H).

後処理

  1. waitAfter 1 h
  2. concentrationthe reaction was concentrated
  3. customthe residue was partitioned between DCM and water
  4. extractionThe aqueous phase was extracted several times with DCM
  5. dry with materialthe combined organic fractions were dried over MgSO
  6. concentrationconcentrated
  7. custompurified via column chromatography (silica, 0-1% MeOH in DCM (1% NH OH))

出典と根拠

ORDレコード
ord-5917f609cdbd4c52817647d5186cd9c8
出典データセット
uspto-grants-2010_04
特許番号
US07691850B2

反応ノート

読み込み中…