Triethylamine → Benzyl (2-fluoro-4-{2-[(4-pyrrolidin-1-ylpiperidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)carbamate

HRID 492764ノート

反応式

HRID 492764 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([F:26])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:35](OC1C=CC=CC=1)=[O:36].[N:44]1([CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)[CH2:48][CH2:47][CH2:46][CH2:45]1>O1CCCC1.O.C(OCC)(=O)C.CN(C)C=O>[F:26][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:35]([N:52]3[CH2:53][CH2:54][CH:49]([N:44]4[CH2:48][CH2:47][CH2:46][CH2:45]4)[CH2:50][CH2:51]3)=[O:36])[CH:7]=2)[CH:14]=[CH:13][C:12]=1[NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

参加物

9

反応物 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

生成物 1

HCID 23153372Benzyl (2-fluoro-4-{2-[(4-pyrrolidin-1-ylpiperidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)carbamate収率 47.5%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (230 mg) in tetrahydrofuran (6.50 ml) was added triethylamine (0.181 ml), and then phenyl chloroformate (0.123 ml) was added dropwise thereto while stirring in an ice bath, followed by stirring for 10 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (2.0 ml) and 4-(1-pyrrolidinyl)piperidine (301 mg) were then added, followed by stirring at room temperature for 11 hrs. To the reaction mixture was added ethyl acetate (50 ml) and water (30 ml) to partition. The organic layer was washed with brine (30 ml×3), and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1) to provide the titled compound (165 mg, 47.5%) as pale yellow powder.

後処理

  1. stirringby stirring for 10 min
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 11 hrs
  5. customto partition
  6. washThe organic layer was washed with brine (30 ml×3)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a residue, which
  10. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent

出典と根拠

ORDレコード
ord-fed1a37c5c9b4576a98fdc64bc7f1f4c
出典データセット
uspto-grants-2009_05
特許番号
US07531532B2

反応ノート

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