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Triethylamine → 3-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20599
ノート
印刷プレビュー

反応式

HRID 20599 の反応式
[F:1][C:2]1[CH:10]=[C:9](F)[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.ClC(N(C)C)=C(C)C.C(N(CC)CC)C.Cl.[NH:29]1[CH2:32][CH2:31][CH2:30]1.[OH:33][C:34]1[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=1)[C:37]([NH:39][C:40]1[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=1)=[O:38].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.Cl.C(#N)C>[N:29]1([C:4]([C:3]2[C:2]([F:1])=[CH:10][C:9]([O:33][C:34]3[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=3)[C:37]([NH:39][C:40]3[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=3)=[O:38])=[C:8]([F:12])[CH:7]=2)=[O:6])[CH2:32][CH2:31][CH2:30]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

10

反応物 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5211702,4,5-Trifluorobenzoic acidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 12308726Azetidine hydrochlorideHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

生成物 1

HCID 11612805
3-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide
収率 31.9%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
160 °C

実験手順

A solution of 2,4,5-trifluorobenzoic acid (123 mg, 0.7 mmol) in DCM (1.7 mL) was treated with (1-chloro-2-methylprop-1-en-1-yl)dimethylamine (103 mg, 0.77 mmol) and stirred under argon for 1 hour. The mixture was then treated with triethylamine (0.29 mL, 2.1 mmol) and azetidine hydrochloride (78 mg, 0.84 mmol), before being left to stir for 18 hours. The mixture was diluted with DCM (5 mL) and 2M hydrochloric acid (4 mL) and separated. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was treated with suspension of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol) and potassium carbonate (284 mg, 2.05 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 1.5 hours. The reaction mixture was filtered and concentrated in vacuo. The residue was then chromatographed on silica, eluting with 0-15% methanol in ethylacetate, to give the title compound (74 mg).

後処理

  1. waitbefore being left
  2. stirringto stir for 18 hours
  3. customseparated
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated in vacuo
  9. customThe residue was then chromatographed on silica
  10. washeluting with 0-15% methanol in ethylacetate

出典と根拠

ORDレコード
ord-ef98e1c7b4764eec9a3f724e10aa14e9
出典データセット
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07745475B2

反応ノート

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