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Benzenamine, 4-(4-morpholinyl)- → 6-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

HRID 2414533
ノート
印刷プレビュー

反応式

HRID 2414533 の反応式
C(OC1C=CC2SC([NH:12][C:13]([C:15]3[O:16][C:17]4[C:22]([C:23](=[O:25])[CH:24]=3)=[CH:21][CH:20]=[CH:19][C:18]=4[N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[O:14])=NC=2C=1)C.[O:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:46]=[CH:45][C:43](N)=[CH:42][CH:41]=2)[CH2:36][CH2:35]1.CN([C:50]([O:54]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:69]1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[N:37]1([C:40]2[CH:46]=[CH:45][C:43]([NH:12][C:13]([C:15]3[O:16][C:17]4[C:22]([C:23](=[O:25])[CH:24]=3)=[CH:21][C:20]([O:54][CH3:50])=[CH:19][C:18]=4[N:26]3[CH2:31][CH2:69][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[O:14])=[CH:42][CH:41]=2)[CH2:38][CH2:39][O:34][CH2:35][CH2:36]1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 757711-HydroxybenzotriazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 235333708-(4-Methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (5-ethoxy-benzothiazol-2-yl)-amide

生成物 1

HCID 235333126-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide
収率 79%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Into a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer is added 327 mg (0.89 mmol, 1.0 equiv.) of 6-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid hydrochloride salt (Reference Example 23). This material is dissolved in 20 mL of DMF and then 189 mg (1.06 mmol, 1.2 equiv.) of 4-morpholinoaniline is added. To the stirred solution is quickly added simultaneously added 568 mg (1.77 mmol, 2.0 equiv.) of TBTU and 239 mg (1.77 mmol, 2.0 equiv.) of HOBT. At this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes. The reaction is allowed to stir at room temperature for 18 hrs, then is concentrated on a rotary evaporator under high vacuum in order to remove the DMF. The residue is triturated with methanol and the crude solids are recovered by filtration. These residues are then purified by flash chromatography using a gradient of 5-10% methanol in methylene chloride as eluent. The eluted material, which is obtained from chromatography, is concentrated, dried under high vacuum, suspended in methylene chloride, dried over K2CO3, concentrated, then crystallized from methanol to give the free base of the pure product as 345 mg (79%) of a yellow solid. Mass Spec.: calc. for [C27H32FN4O5+H]+ Theor. m/z=393; Obs.=393.

後処理

  1. customInto a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer
  2. additionAt this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes
  3. concentrationis concentrated on a rotary evaporator under high vacuum in order
  4. customto remove the DMF
  5. customThe residue is triturated with methanol
  6. filtrationthe crude solids are recovered by filtration
  7. customThese residues are then purified by flash chromatography
  8. customThe eluted material, which is obtained from chromatography
  9. concentrationis concentrated
  10. customdried under high vacuum
  11. dry with materialdried over K2CO3
  12. concentrationconcentrated
  13. customcrystallized from methanol

出典と根拠

ORDレコード
ord-9cd62f72f5dd4c0e81ce7806a90f9efe
出典データセット
uspto-grants-2004_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06812225B2

反応ノート

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