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Ammonia → 2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetic acid

HRID 2237626
ノート
印刷プレビュー

反応式

HRID 2237626 の反応式
Cl[C:2]1[C:7]2[C:8](=[O:31])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]([O:28]C)=[O:27])[CH2:21][CH2:20]4)=[CH:15][C:14]=3[F:30])[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.[Li+].[OH-].Cl.C(O)(C)C.[NH3:39]>O1CCOCC1.C1COCC1.CO.O.C(Cl)Cl>[NH2:39][C:2]1[C:7]2[C:8](=[O:31])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]4[CH2:20][CH2:21][CH:22]([CH2:25][C:26]([OH:28])=[O:27])[CH2:23][CH2:24]4)=[CH:15][C:14]=3[F:30])[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=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

9

反応物 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 3939Lithium HydroxideHCID 59302529methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate

生成物 1

HCID 59302526
2-(4-(4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetic acid

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒HCID 21892291Methanol tetrahydrofuran water溶媒

反応条件

温度
23 °C

実験手順

The title compound was prepared as follows. A mixture of methyl 2-(4-(4-(4-chloro-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)-3-fluorophenyl)cyclohexyl)acetate (20 mg, 0.045 mmol), from Preparation 4, in 0.5M ammonia in dioxane was stirred at 50° C., in a tightly capped flask, for 3 hours. The reaction mixture was concentrated to give a white solid, which was carried on to the next step without further purification. LiOH (4.5 mg, 0.18 mmol) was added to a solution of the white solid in THF/methanol/water (2.4 mL, 3:2:1) and the resulting solution was stirred at 23° C. for 16 hours. 1M HCl solution was added to reaction solution to adjust the pH about 3. 20% i-propanol in DCM (30 mL) was added to extract reaction mixture. The organic layer was separated and dried over MgSO4 and concentrated to give a solid. Purification was done by chromatography (4 g, silica gel column) with methanol/DCM from 2-6% to give a white solid 12 mg as the title compound.

後処理

  1. customfrom Preparation 4
  2. concentrationThe reaction mixture was concentrated
  3. customto give a white solid, which
  4. customwas carried on to the next step without further purification
  5. extractionto extract
  6. customreaction mixture
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customto give a solid
  11. customPurification

出典と根拠

ORDレコード
ord-1e8f50ea10b04d3e95bed99987a192bb
出典データセット
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07718645B2

反応ノート

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