Cesium carbonate → 5-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-one

HRID 2069728Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:12][N:11]([CH3:13])[CH2:10]2)=[CH:4][N:3]=1.[NH2:14][C:15]1[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=[C:19]([Br:21])[CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.O>[Br:21][C:19]1[CH:20]=[C:15]([NH:14][C:2]2[CH:7]=[CH:6][C:5]([O:8][CH:9]3[CH2:12][N:11]([CH3:13])[CH2:10]3)=[CH:4][N:3]=2)[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-Bromo-5-(1-methyl-azetidin-3-yloxy)-pyridine (0.327 g, 1.32 mmol) and 3-Amino-5-bromo-1-methyl-1H-pyridin-2-one (0.321 g, 1.58 mmol) in dioxane (5.5 mL) add Cs2CO3 (0.645 g, 1.98 mmol), xantphos (0.153 g, 0.264 mmol) and bubbled argon through reaction mixture for 15 min. Add Pd (OAc)2 (0.03 g, 0.132 mmol) in the end. The reaction was heated at 100° C. under argon for 3 h. TLC shows 2-Bromo-5-(1-methyl-azetidin-3-yloxy)-pyridine was gone. The reaction mixture was treated with water (30 mL) and extracted with dichloromethane (3×20 mL). Organic phase was concentrated and loaded onto silica gel column separation. Using 3-5% MeOH in DCM gave 5-bromo-1-methyl-3-[5-(1-methyl-azetidin-3-yloxy)-pyridin-2-ylamino]-1H-pyridin-2-one as green solid (200 mg, 40% yield).

Workup

custombubbled argon
customthrough reaction mixture for 15 min
extractionextracted with dichloromethane (3×20 mL)
concentrationOrganic phase was concentrated and loaded onto silica gel column separation

Sources & evidence

ORD record: ord-e7ca2f13f9b841369868c214c49900e0
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299077B2

Reaction notes

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