Sodium Iodide → (R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholine

HRID 1465841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1465841
[CH3:1][S-:2].[Na+].CS(O[CH2:9][C:10]1[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[CH3:22])[N:13]=[C:12]([Cl:23])[N:11]=1)(=O)=O.ClC1N=C(N2CCOC[C@H]2C)C=C(CCl)N=1.[I-].[Na+]>CC#N.CCOC(C)=O>[Cl:23][C:12]1[N:13]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[CH3:22])[CH:15]=[C:10]([CH2:9][S:2][CH3:1])[N:11]=1

Komponenten

7

Edukt 4

HCID 5238Sodium IodideHCID 4378561Sodium methanethiolateHCID 86651636(R)-(2-chloro-6-(3-methylmorpholino)pyrimidin-4-yl)methyl methanesulfonateHCID 86660211(R)-4-(2-chloro-6-(chloromethyl)pyrimidin-4-yl)-3-methylmorpholine

Produkt 1

HCID 86660210(R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholineAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

In a 3 L fixed vessel, sodium thiomethoxide (21% in water) (216 g, 646.69 mmol) was added dropwise over 5 minutes to a stirred solution of a mixture of approximately two thirds (R)-(2-chloro-6-(3-methylmorpholino)pyrimidin-4-yl)methyl methanesulfonate and one third (R)-4-(2-chloro-6-(chloromethyl)pyrimidin-4-yl)-3-methylmorpholine (130.2 g, 431 mmol) and sodium iodide (1.762 ml, 43.11 mmol) in MeCN (1 L) at RT (temperature dropped from 20° C. to 18° C. over the addition and then in the next 5 minutes rose to 30° C.). The reaction mixture was stirred for 16 hours and then diluted with EtOAc (2 L), and washed sequentially with water (750 ml) and saturated brine (1 L). The organic layer was dried over MgSO4, filtered and then evaporated to afford (R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholine (108 g, 91%); 1H NMR (400 MHz, DMSO-d6) 1.20 (3H, d), 2.07 (3H, s), 3.11-3.26 (1H, m), 3.44 (1H, td), 3.53 (2H, s), 3.59 (1H, dd), 3.71 (1H, d), 3.92 (1H, dd), 3.92-4.04 (1H, br s), 4.33 (1H, s), 6.77 (1H, s); m/z: (ES+) MH+, 274.36.

Aufarbeitung

  1. additiondropped from 20° C. to 18° C. over the addition
  2. customin the next 5 minutes
  3. customrose to 30° C.
  4. washwashed sequentially with water (750 ml) and saturated brine (1 L)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-39da1f17ffef41e4a07e8570c2431b6e
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US08999997B2

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