Diisopropylamine → tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate

HRID 1922828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1922828
C(NC(C)C)(C)C.[Li]CCCC.COP([CH2:19][C:20]1[N:21]([CH3:36])[C:22]2[C:27]([N:28]=1)=[C:26]([N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)[N:25]=[C:24]([Cl:35])[N:23]=2)(=O)OC.[C:37]([O:41][C:42]([N:44]1[CH2:47][C:46](=O)[CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38]>C1COCC1>[C:37]([O:41][C:42]([N:44]1[CH2:47][C:46](=[CH:19][C:20]2[N:21]([CH3:36])[C:22]3[C:27]([N:28]=2)=[C:26]([N:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)[N:25]=[C:24]([Cl:35])[N:23]=3)[CH2:45]1)=[O:43])([CH3:40])([CH3:38])[CH3:39]

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 59605250dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonateHCID 178418339Butyllithium

Produkt 1

HCID 59605709tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylateAusbeute 92,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a solution of diisopropylamine (1.4 mL, 9.8 mmol) in THF (3 mL) at −78° C. was added n-BuLi (3.9 mL, 9.8 mmol, 2.5 M in hexanes) and the resulting mixture allowed to stir for 20 min. The resulting solution was added to a pale green solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl)phosphonic acid dimethyl ester (3.36 g, 8.9 mmol) in THF (80 mL) at −78° C. The resulting mixture was warmed to r.t. before a solution of 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.76 g, 10.2 mmol) in THF (10 mL) was added. The resulting pink mixture was stirred for 16 h then quenched with H2O. The mixture was concentrated in vacuo and the residue was partitioned between DCM and brine. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-70%) affording the title compound as a green powder (3.46 g, 92%). 1H NMR (CDCl3, 400 MHz): δ 6.33-6.32 (1 H, m), 4.91-4.90 (2 H, m), 4.71-4.70 (2 H, m), 4.28 (4 H, brd s), 3.81 (4 H, t, J=4.74 Hz), 3.71 (3 H, s), 1.48 (9 H, s).

Aufarbeitung

  1. additionwas added
  2. stirringThe resulting pink mixture was stirred for 16 h
  3. customthen quenched with H2O
  4. concentrationThe mixture was concentrated in vacuo
  5. customthe residue was partitioned between DCM and brine
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-70%)

Quellen und Nachweise

ORD-Eintrag
ord-72593db4c04049dfa1ea8b734a7dd0bc
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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