Hydrochloric Acid → 1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea

HRID 868888

Reaktionsgleichung

Reaktionsgleichung von HRID 868888
C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)[C:3](=[O:4])C1.N1C=CC=CC=1.[NH2:25][C:26]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:27]=1[CH2:28][NH:29][C:30](=[O:37])[N:31]2[CH3:36].C(N(CC)C(C)C)(C)C.O[C@H](C1C=CC=CC=1)C([O-])=O.[CH3:58][C:59]1([CH3:70])[CH2:68][C@@H:67]([NH2:69])[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[O:60]1.Cl>CCOC(C)=O.C(#N)C>[CH3:58][C:59]1([CH3:70])[CH2:68][C@@H:67]([NH:69][C:3]([NH:25][C:26]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:27]=2[CH2:28][NH:29][C:30](=[O:37])[N:31]3[CH3:36])=[O:4])[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[O:60]1

Komponenten

10

Edukt 7

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 81531DiisopropylethylamineHCID 676246Di(succinimido) carbonateHCID 5460269(R)-MandelateHCID 42157625(R)-2,2-dimethylchroman-4-amineHCID 574159275-amino-1-methyl-3,4-dihydroquinazolin-2(1H)-one

Produkt 1

HCID 716114831-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)ureaAusbeute 88,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A slurry of N,N-disuccinimidyl carbonate (434 mg, 1.69 mmol), acetonitrile (6 mL), pyridine (0.137 mL, 1.69 mmol), and 5-amino-1-methyl-3,4-dihydroquinazolin-2(1H)-one (A-1) (300 mg, 1.69 mmol) was stirred at room temperature. After 45 min, N,N-diisopropylethylamine (0.879 mL, 5.08 mmol) and (R)-2-hydroxy-2-phenylacetate salt of (R)-2,2-dimethylchroman-4-amine (B-2) (558 mg, 1.69 mmol) were added. After 30 minutes, EtOAc (50 mL) and 2N aqueous HCl (20 mL) were added and the layers separated. The organic extract was washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (0-10% MeOH/EtOAc gradient) to afford the title compound (565 mg, 1.49 mmol, 88% yield). 1H NMR (300 MHz, DMSO-d6) δ 7.80 (s, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.25 (t, J=10.7 Hz, 1H), 7.16 (dd, J=16.6, 8.2 Hz, 3H), 6.89 (t, J=7.0 Hz, 1H), 6.73 (d, J=8.6 Hz, 2H), 6.63 (d, J=8.1 Hz, 1H), 4.94 (dd, J=15.2, 10.0 Hz, 1H), 4.18 (s, 2H), 3.14 (s, 3H), 2.13 (dd, J=13.2, 6.2 Hz, 1H), 1.69 (dd, J=30.9, 18.0 Hz, 1H), 1.39 (s, 3H), 1.27 (s, 3H). MS (ESI+) m/z 449 (M+H)+.

Aufarbeitung

  1. waitAfter 30 minutes
  2. customthe layers separated
  3. extractionThe organic extract
  4. washwas washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-10% MeOH/EtOAc gradient)

Quellen und Nachweise

ORD-Eintrag
ord-c2f3ef860df64005a91eeb46460def2f
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969325B2

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