Reaction #166301

Reaction equation

Sodium 2-methylpropan-2-olate

compound 4

9-Cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine

XANTPHOS

NH4Cl

2,5-dibromo-3-methylpyridine

→

N-(5-bromo-3-methyl-2-pyridinyl)-9-cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   OtherThe reaction mixture was degassed
2. 2
   Otherby bubbling nitrogen through the solution for ˜1 mM
3. 3
   Othermicrowave irradiation for 1 hour
4. 4
   Extractionextracted with 10% isopropanol/DCM
5. 5
   DryingThe organic layer was dried with MgSO4
6. 6
   Concentrationconcentrated in vacuum
7. 7
   OtherPurification by flash column chromatography
8. 8
   Washeluting with a gradient of DCM-5% methanol/DCM provided compound 77 as a yellow solid (150 mg, 71%)

Procedure

Sodium 2-methylpropan-2-olate (0.142 g, 1.48 mmol) was combined with compound 4 (0.125 g, 0.493 mmol) and 2,5-dibromo-3-methylpyridine (0.149 g, 0.592 mmol) in 1,4-dioxane (3 ml). The reaction mixture was degassed by bubbling nitrogen through the solution for ˜1 mM, followed by the addition of XANTPHOS (0.0428 g, 0.0740 mmol) and Pd2(dba)3 (0.0339 g, 0.0370 mmol). The reaction was heated to 140° C. using microwave irradiation for 1 hour. The reaction mixture was poured into sat. NH4Cl and extracted with 10% isopropanol/DCM. The organic layer was dried with MgSO4 and concentrated in vacuum. Purification by flash column chromatography, eluting with a gradient of DCM-5% methanol/DCM provided compound 77 as a yellow solid (150 mg, 71%). LCMS-ESI (POS), M/Z, M+1: Found 423.1

Source