2-Bromopyrimidine → 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-1-pyrimidin-2-yl-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a glass vial was added 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine dihydrochloride (prepared using step 1 of example 91 from intermediate 13) (75 mg, 0.16 mmol), 2-bromopyrimidine (55 mg, 0.342 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.85 mmol). The vial was capped and the mixture heated in the microwave at 160° C. for 20 min. Purification by reverse phase Gilson HPLC (Method A) and subsequent neutralization of the combined fractions over PL-HCO3 MP to give 6-(6-methoxy-5-trifluoromethyl-pyridin-3-yl)-4-((S)-1-pyrimidin-2-yl-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine as a brown solid (17 mg, 21% yield) 1H NMR (400 MHz, DMSO-d6, 298K) δ ppm 2.23-2.43 (m, 2 H) 2.85-2.99 (t, 2 H) 3.22-3.94 (m, 9 H) 4.08-4.27 (m, 2 H) 5.70-5.80 (m, 1 H) 6.56-6.66 (t, 1 H) 7.76-7.87 (m, 1 H) 8.12-8.27 (m, 1 H) 8.28-8.42 (m, 2 H) 8.59-8.68 (m, 1 H) LCMS: [M+H]+=474.2, Rt(1)=1.91 min.

Provenance & Evidence