Sodium Bicarbonate → 7-methyl-5-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1909919Notes

Reaction equation

HRID 1909919 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11](=[O:19])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[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:44]1[C:52]2[C:51]([NH2:53])=[N:50][CH:49]=[N:48][C:47]=2[N:46]([CH3:54])[CH:45]=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.CCOCC.O1CCOCC1>[CH3:54][N:46]1[C:47]2[N:48]=[CH:49][N:50]=[C:51]([NH2:53])[C:52]=2[C:44]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11](=[O:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:6][CH2:5]3)=[CH:45]1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 665609385-Bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 668241055-bromo-1-(phenylacetyl)-2,3-dihydro-1H-indole

Product 1

HCID 534667277-methyl-5-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 13%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 5-bromo-1-(phenylacetyl)-2,3-dihydro-1H-indole (139 mg, 0.440 mmol), bis(pinacolato)diboron (117 mg, 0.462 mmol), and potassium acetate (130 mg, 1.321 mmol) was added 1,4-dioxane (6 mL), and the mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (19.08 mg, 0.023 mmol) was added, and the reaction mixture was stirred for 3 hours at 100 C into a sealed vessel. The reaction was cooled down to room temperature. 5-bromo-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (100 mg, 0.440 mmol) and sat. aq. NaHCO3 (2 mL) were added, and N2 gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (17.98 mg, 0.022 mmol) was added, the vessel was sealed, and the reaction mixture was stirred for 3 days at 100 C). The mixture was allowed to cool to room temperature and poured onto water (˜150 mL). The resulting mixture was filtered. The solid in the filter was mixed with a 80:20 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 product. Trituration with Et2O afforded the title compound 7-methyl-5-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (22 mg) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 3.21 (t, J=8.21 Hz, 2H), 3.73 (s, 3H), 3.87 (s, 2H), 4.21 (t, J=8.46 Hz, 2H), 7.15-7.42 (m, 8H), 8.11-8.15 (m, 2H)

Workup

  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 for 3 days at 100 C)
  5. temperatureto cool to room temperature
  6. additionpoured onto water (˜150 mL)
  7. filtrationThe resulting mixture was filtered
  8. additionThe solid in the filter was mixed with a 80:20 mixture of CHCl3
  9. filtrationCH3OH (˜7 mL), and the resulting mixture was filtered
  10. customFlash chromatography on SiO2 (gradient: 100% CHCl3 to 90:10:1 CHCl3:CH3OH:NH4OH) provided the product

Sources & evidence

ORD record
ord-d5bba4b69236488ca9703e705cbdc891
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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