Sodium Hydroxide → (4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

HRID 2353062Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2353062
[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]45[CH2:25][CH2:24][C:21]([CH2:26][C:27]([O:29]C)=[O:28])([CH2:22][CH2:23]4)[CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Na+]>CO.C1COCC1>[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:13]=[CH:14][C:15]([C:18]45[CH2:23][CH2:22][C:21]([CH2:26][C:27]([OH:29])=[O:28])([CH2:20][CH2:19]4)[CH2:24][CH2:25]5)=[CH:16][CH:17]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

Komponenten

5

Edukt 2

HCID 14798Sodium Hydroxide2×HCID 25258352methyl {4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

Produkt 1

HCID 16202164(4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of methyl {4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (122 mg, 0.28 mmol) in MeOH (10 mL) and THF (5 mL) was added 2M NaOH (0.7 mL). The reaction mixture was stirred at ambient temperature overnight then further 2M NaOH (0.7 mL) was added and the reaction mixture heated to 50° C. for 5 hrs. The mixture was allowed to cool, the solvent was removed under reduced pressure and the residue was acidified to pH 2 with 2M HCl and the suspension filtered and dried. The product was purified on a basic reverse phase preparative HPLC system loading in NMP (˜2 mL), water (˜2 mL) and 1-2 drops of 0.88 ammonia, and eluting with 13-40% water (+1% NH3)-MeCN, to provide the title compound as a solid, 40 mg (0.0952 mmol, 34%).

Aufarbeitung

  1. temperaturethe reaction mixture heated to 50° C. for 5 hrs
  2. temperatureto cool
  3. customthe solvent was removed under reduced pressure
  4. filtrationthe suspension filtered
  5. customdried
  6. customThe product was purified on a basic reverse phase preparative HPLC system loading in NMP (˜2 mL)
  7. washwater (˜2 mL) and 1-2 drops of 0.88 ammonia, and eluting with 13-40% water (+1% NH3)-MeCN

Quellen und Nachweise

ORD-Eintrag
ord-90f0bc95499c46a2a4d03b6dbdba3aad
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07749997B2

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