Pyridine → 3,3-dimethyl-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2,3-dihydrobenzofuran-6-carboxamide

HRID 1256407Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1256407
[CH3:1][C:2]1([CH3:14])[C:6]2[CH:7]=[CH:8][C:9]([C:11](Cl)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3]1.N1C=CC=CC=1.[CH3:21][C:22]1[CH:37]=[C:25]2[N:26]=[C:27]([NH2:36])[CH:28]=[C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:24]2[N:23]=1>C(#N)C.O>[CH3:1][C:2]1([CH3:14])[C:6]2[CH:7]=[CH:8][C:9]([C:11]([NH:36][C:27]3[CH:28]=[C:29]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[N:24]4[N:23]=[C:22]([CH3:21])[CH:37]=[C:25]4[N:26]=3)=[O:12])=[CH:10][C:5]=2[O:4][CH2:3]1

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 582071812-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amineHCID 866522793,3-Dimethyl-2,3-dihydrobenzofuran-6-carbonyl chloride

Produkt 1

HCID 670643233,3-dimethyl-N-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2,3-dihydrobenzofuran-6-carboxamideAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

In a 25 ml pear flask containing crude 3,3-dimethyl-2,3-dihydrobenzofuran-6-carbonyl chloride (25 mg, 0.12 mmol) was added pyridine (1 mL), immediately followed by 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 26.9 mg, 0.120 mmol). The mixture was stirred at room temperature for ˜16 h. The reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate, and the aqueous layer was extracted one more time with ethyl acetate. Combined organic layers were washed once more with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by SiO2 (20% EtOAc, second spot from the top) to give an off-white solid. To facilitate transfer of the small amount of product, the solid was dissolved in 0.5 mL of acetonitrile, and then suspended in 15 mL of water. Lyophilization of the mixture gave the titled product (5.1 mg, 11% yield). 1H NMR (CHLOROFORM-d) δ: 8.58 (s, 1H), 8.08-8.15 (m, 3H), 7.53-7.59 (m, 3H), 7.46 (dd, J=7.7, 1.6 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 6.28 (s, 1H), 4.31-4.34 (m, 2H), 2.50 (s, 3H), 1.36-1.42 (m, 6H); ESI-MS: m/z 399.4 (M+H)+.

Aufarbeitung

  1. customThe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  2. extractionthe aqueous layer was extracted one more time with ethyl acetate
  3. washCombined organic layers were washed once more with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by SiO2 (20% EtOAc, second spot from the top)
  8. customto give an off-white solid

Quellen und Nachweise

ORD-Eintrag
ord-d939e4d7b4384ae888d12c3da7d74e95
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461163B2

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