Sodium Carbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 475974ノート

反応式

HRID 475974 の反応式
Cl[C:2]1[CH:3]=[C:4]([C:15]([NH:17][CH2:18][C:19]2[C:20](=[O:27])[NH:21][C:22]([CH3:26])=[CH:23][C:24]=2[CH3:25])=[O:16])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=1.[CH3:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37][N:36]=2)[CH2:31][CH2:30]1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[CH3:25][C:24]1[CH:23]=[C:22]([CH3:26])[NH:21][C:20](=[O:27])[C:19]=1[CH2:18][NH:17][C:15]([C:4]1[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH:12]([CH3:14])[CH3:13])[C:6]=2[N:7]=[C:2]([C:38]2[CH:37]=[N:36][C:35]([N:32]3[CH2:31][CH2:30][N:29]([CH3:28])[CH2:34][CH2:33]3)=[CH:40][CH:39]=2)[CH:3]=1)=[O:16]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 565974266-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

生成物 1

HCID 56597428N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-6-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 679Dimethyl Sulfoxide溶媒

実験手順

To a 10-mL microwave vial were added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (70 mg, 0.180 mmol),1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (71.1 mg, 0.235 mmol), DMSO (2.0 mL) and sodium carbonate (0.271 mL, 0.541 mmol) and the mixture was degassed for 10 min under nitrogen. Bis(triphenylphosphine)palladium(II) chloride (10.13 mg, 0.014 mmol) was added and the contents were sealed. The mixture was irradiated (microwave) at 140° C. for 8 h. The reaction mixture was then quenched with water (5 mL) and filtered. The crude product was washed with water, dried, and then purified via silica gel chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM). The resulting product was treated with MeOH and 1N HCl. The mixture was concentrated in vacuo, dried under high vacuum and collected as the HCl salt, 42 mg (36%). LCMS E-S (M+H)=529.0 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (d, 6H), 2.13 (s, 3H), 2.25 (s, 3H), 2.42 (s, 3H), 2.81 (d, J=4.55 Hz, 3H), 3.03-3.21 (m, 2H), 3.41 (br. s., 2H), 3.52 (d, J=11.37 Hz, 2H), 4.39 (d, J=5.05 Hz, 2H), 4.56 (d, J=14.40 Hz, 2H), 5.23 (quin, J=6.63 Hz, 1H), 5.91 (s, 1H), 7.19 (d, J=9.09 Hz, 1H), 7.68 (s, 1H), 8.50 (dd, J=9.09, 2.27 Hz, 1H), 8.73 (t, J=4.93 Hz, 3H), 8.98 (d, J=2.02 Hz, 3H), 10.97-11.21 (m, 2H)

後処理

  1. customthe mixture was degassed for 10 min under nitrogen
  2. customthe contents were sealed
  3. customThe mixture was irradiated (microwave) at 140° C. for 8 h
  4. customThe reaction mixture was then quenched with water (5 mL)
  5. filtrationfiltered
  6. washThe crude product was washed with water
  7. customdried
  8. custompurified via silica gel chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM)
  9. additionThe resulting product was treated with MeOH and 1N HCl
  10. concentrationThe mixture was concentrated in vacuo
  11. customdried under high vacuum
  12. customcollected as the HCl salt, 42 mg (36%)

出典と根拠

ORDレコード
ord-1c3faba957c14ac59a0f1077d9bfaed0
出典データセット
uspto-grants-2014_01
特許番号
US08637509B2

反応ノート

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