3-Chloro-4-pyridineboronic acid → 5-(3-Chloro-pyridin-4-yl)-N4-(tetrahydro-pyran-4-yl)-pyrimidine-2,4-diamine

HRID 875944

Reaction equation

Br[C:2]1[C:3]([NH:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Cl:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][C:22]=1B(O)O>O1CCOCC1.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>[Cl:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][C:22]=1[C:2]1[C:3]([NH:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of compound 33 (2.03 g, 7.43 mmol), 3-chloropyridin-4-ylboronic acid (3.51 g, 22.3 mmol), and Pd(PPh3)2Cl2 (0.522 g, 0.743 mmol) in dioxane (44 ml) in a pressure vessel was purged with N2 for 20 minutes and to this mixture was added aq. Na2CO3 (1 M, 22 mL) by syringe. The reaction was further purged with N2 for another 20 minutes and then heated to 130° C. for 12 hours. DCM was added to the reaction and the mixture was washed with water and brine. The organic layer was dried with sodium sulfate and concentrated to provide compound 34 (2.07 g, crude, 98%) which was used in the next reaction without further purification. LCMS-ESI (POS), M/Z, M+1: Found 306.1, Calculated 306.1.

Workup

customwas purged with N2 for 20 minutes and to this mixture
additionwas added aq. Na2CO3 (1 M, 22 mL) by syringe
customThe reaction was further purged with N2 for another 20 minutes
additionDCM was added to the reaction
washthe mixture was washed with water and brine
dry with materialThe organic layer was dried with sodium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-4ffe5995e4ef4227aa7e7f5e8e681efe
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980903B2

Linked notes

Loading…