Phosphorus oxychloride → HCID 178464493, Verbindung

HRID 2169184

Reaktionsgleichung

Reaktionsgleichung von HRID 2169184
[CH2:1]([O:8][C:9]1[C:10]([C:29]([OH:31])=O)=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:32]([O:39][CH2:40][CH2:41][NH:42][CH:43]([CH3:48])[C:44]([F:47])([F:46])[F:45])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O=P(Cl)(Cl)Cl.C(O)CO.C(=O)=O>N1C=CC=CC=1.O>[CH2:1]([O:8][C:9]1[C:10]([C:29]([N:42]([CH2:41][CH2:40][O:39][Si:32]([C:35]([CH3:36])([CH3:38])[CH3:37])([CH3:34])[CH3:33])[CH:43]([CH3:48])[C:44]([F:46])([F:45])[F:47])=[O:31])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 24813Phosphorus oxychlorideHCID 86601574Dry ice ethyleneglycolHCID 86725834N-(2-(tert-butyldimethylsilyloxy)ethyl)-1,1,1-trifluoropropan-2-amineHCID 178524871HCID 178524871, Verbindung

Produkt 1

HCID 178464493HCID 178464493, VerbindungAusbeute 58,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 5-(benzyloxy)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxypyrimidine-4-carboxylic acid (28-02) (150 mg, 342 μmol, Eq: 1.00) and N-(2-(tert-butyldimethylsilyloxy)ethyl)-1,1,1-trifluoropropan-2-amine (41) (102 mg, 376 μmol, Eq: 1.1) in pyridine (1.5 ml) was added POCl3 (157 mg, 95.6 μl, 1.03 mmol, Eq: 3.00) at −10° C. (ethylene glycol-dry-ice bath), then the reaction mixture was stirred at 0° C. for 2 hr. Ice cooled-water was slowly added to the reaction mixture at 0° C., which was extracted with ethyl acetate. The organic layer was washed with aqueous saturated NaHCO3 solution, dried (MgSO4), concentrated, and chromatographed (silica gel, gradient 5 to 50% ethyl acetate-hexane) to obtain 5-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxy-N-(1,1,1-trifluoropropan-2-yl)pyrimidine-4-carboxamide (42) (oil, 138 mg, 199 μmol, 58.3% yield).

Aufarbeitung

  1. additionwas slowly added to the reaction mixture at 0° C.
  2. extractionwhich was extracted with ethyl acetate
  3. washThe organic layer was washed with aqueous saturated NaHCO3 solution
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customchromatographed (silica gel, gradient 5 to 50% ethyl acetate-hexane)

Quellen und Nachweise

ORD-Eintrag
ord-afe21fbb8ac64f81b1509f78d6360f15
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045486B2

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