Triethylamine → (R)-(-)-methanesulfonic acid 3-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]-2-methylpropyl ester

HRID 1157462Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157462
[OH:1][CH2:2][C@H:3]([CH3:32])[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)[N:10]([CH2:24][C:25]([NH:27][CH:28]([CH3:30])[CH3:29])=[O:26])[C:9]2=[O:31].[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C>ClCCl.C(OCC)(=O)C>[CH:28]([NH:27][C:25]([CH2:24][N:10]1[C:9](=[O:31])[C:8]2[C:13](=[CH:14][CH:15]=[C:6]([O:5][CH2:4][C@@H:3]([CH3:32])[CH2:2][O:1][S:34]([CH3:33])(=[O:36])=[O:35])[CH:7]=2)[N:12]=[C:11]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)=[O:26])([CH3:29])[CH3:30]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59511775HCID 59511775, Verbindung

Produkt 1

HCID 59511753(R)-(-)-methanesulfonic acid 3-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]-2-methylpropyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a suspension of (S)-(+)-2-[6-(3-hydroxy-2-methylpropoxy)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (0.96 g, 2.18 mmol) in dichloromethane (100 mL) cooled to −78° C. under argon was added methanesulfonyl chloride (2.50 g, 1.7 mL, 21.90 mmol) dropwise over 5 min, followed by dropwise addition (10 min) of triethylamine (2.21 g, 3.10 mL, 21.9 mmol). The reaction mixture was warmed to −30° C. over 60 min followed by warming to room temperature over 15 min after which time the reaction was found to be complete (HPLC monitoring). The reaction mixture was diluted with ethyl acetate (300 mL), poured into ice water (100 mL) and the organic phase washed with 1N HCl (aq.) (2×200 mL), sat. NaHCO3 (aq.) (1×200 mL) and brine (1×200 mL). The organic phase was dried (MgSO4) and concentrated in vacuo to afford (R)-(−)-methanesulfonic acid 3-[3-(isopropylcarbamoylmethyl)-2-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yloxy]-2-methylpropyl ester as a pale yellow solid (1.13 g, 2.18 mmol, 100%, 91% purity by LC-MS).

Aufarbeitung

  1. temperatureThe reaction mixture was warmed to −30° C. over 60 min
  2. temperatureby warming to room temperature over 15 min after which time the reaction
  3. washthe organic phase washed with 1N HCl (aq.) (2×200 mL), sat. NaHCO3 (aq.) (1×200 mL) and brine (1×200 mL)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-af2e800845a54918b98b2ec9ffe52fbc
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807686B2

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