Tetrahydrofuran → (S)-methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472865Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 472865
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C@H:23]([OH:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Komponenten

6

Edukt 3

HCID 8028TetrahydrofuranHCID 66693787Methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene

Produkt 1

HCID 66693161(S)-methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

To a stirred solution of methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.103 g, 0.123 mmol) and 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.025 ml, 0.025 mmol) in toluene (5 mL) at −35 C was added dropwise 1M catecholoborane/THF (0.245 ml, 0.245 mmol) over 5 min. After 30 min, the reaction mixture was warmed to −15° C., diluted with EtOAc (10 ml) and quenched with sat. Na2CO3 (5 mL). The resulting mixture was vigorously stirred for 30 min, aqueous layer removed and organic layer washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated to yellow residue which was purified by prep-HPLC to afford (S)-methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate as white solid. To a stirred solution above solid (18 mg) in CH2Cl2 (3 mL) and tert-BuOAc (1 mL) was added 70% perchloric acid (0.025 mL) at rt and sealed for 1.5 h. Then, the reaction was diluted with Et2O (25 mL), washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered and concentrated to give yellow solid which was purified by prep-HPLC to afford (S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (0.01 g, 0.021 mmol, 17.06% yield) as pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.86-7.83 (m, 1H), 7.73 (dt, J=6.6, 1.7 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 7.40 (dd, J=12.5, 7.9 Hz, 2H), 7.32-7.27 (m, 2H), 6.86 (s, 1H), 5.14 (s, 1H), 3.80 (s, 3H), 2.65 (s, 3H), 2.51 (s, 3H), 0.95 (s, 9H). LCMS (M+H) calcd for C27H29ClN3O3: 478.19. found: 480.3.

Aufarbeitung

  1. customquenched with sat. Na2CO3 (5 mL)
  2. customaqueous layer removed
  3. washorganic layer washed with sat. Na2CO3 (2×5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to yellow residue which
  7. customwas purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-79533651c83a47a6ada896c2fb6f3bab
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633200B2

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