Sodium Bicarbonate → 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1909914ノート

反応式

HRID 1909914 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11](=[O:21])[CH2:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[F:20])[CH2:6][CH2:5]2.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:46]1[C:54]2[C:49](=[N:50][CH:51]=[N:52][C:53]=2[NH2:55])[N:48]([CH3:56])[N:47]=1.C([O-])(O)=O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[F:20][C:14]1[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=1[CH2:12][C:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:46]3[C:54]4[C:49](=[N:50][CH:51]=[N:52][C:53]=4[NH2:55])[N:48]([CH3:56])[N:47]=3)=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)=[O:21]

参加物

8

反応物 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 127789343-Bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 668238625-bromo-1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indole

生成物 1

HCID 534667253-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine収率 83.8%

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒2 回HCID 312751,4-Dioxane溶媒

実験手順

To a mixture of 5-bromo-1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indole (160 mg, 0.454 mmol), bis(pinacolato)diboron (127 mg, 0.500 mmol), and potassium acetate (134 mg, 1.363 mmol) was added 1,4-dioxane (6 mL), and the mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (18.55 mg, 0.023 mmol) was added, and the reaction mixture was stirred for 3 hours at 100 C in a sealed vessel. The reaction was cooled down to room temperature. 3-bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (104 mg, 0.454 mmol) and sat. aq. NaHCO3 (2 mL) were added, and N2 gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (18.55 mg, 0.023 mmol) was added, the vessel was sealed, and the reaction mixture was stirred overnight at 100 C (LCMS:N13207-34suzu). The mixture was allowed to cool to room temperature and poured onto water (˜150 mL). The resulting mixture was filtered, and the resulting solid was triturated with Et2O. To the solid in the filter was added a 90:10 mixture of CHCl3:CH3OH (˜7 mL), and the resulting mixture was filtered. The filtrate was injected into a 90 g SiO2 columns. Flash chromatography on SiO2 (gradient: 100% CHCl3 to 90:10:1 CHCl3:CH3OH:NH4OH) provided the title compound 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (160 mg) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 3.29 (t, J=8.34 Hz, 2H), 3.94 (s, 3H), 3.97 (s, 2H), 4.30 (t, J=8.46 Hz, 2H), 7.14-7.31 (m, 3H), 7.44 (d, J=8.34 Hz, 1H), 7.53 (s, 1H), 8.14 (d, J=8.34 Hz, 1H), 8.25 (s, 1H)

後処理

  1. customthe mixture was degassed with N2 for 10 minutes
  2. customN2 gas was bubbled through the mixture for 10 minutes
  3. customthe vessel was sealed
  4. stirringthe reaction mixture was stirred overnight at 100 C (LCMS:N13207-34suzu)
  5. temperatureto cool to room temperature
  6. additionpoured onto water (˜150 mL)
  7. filtrationThe resulting mixture was filtered
  8. customthe resulting solid was triturated with Et2O
  9. additionTo the solid in the filter was added
  10. additiona 90:10 mixture of CHCl3
  11. filtrationCH3OH (˜7 mL), and the resulting mixture was filtered

出典と根拠

ORDレコード
ord-259dbf1f544742c48fb441718def9cb2
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

反応ノート

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