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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
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HRID 2237626 반응식
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
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참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매HCID 21892291Methanol tetrahydrofuran water용매

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온도
23 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1e8f50ea10b04d3e95bed99987a192bb
출처 데이터셋
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07718645B2

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