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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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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2237626
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
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittelHCID 21892291Methanol tetrahydrofuran waterLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1e8f50ea10b04d3e95bed99987a192bb
Quelldatensatz
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07718645B2

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