1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one → HCID 68738797, compound

HRID 869927Notes

Reaction equation

HRID 869927 reaction equation
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]1=[O:17].Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]([C:28]2([C:31]3[CH:41]=[CH:40][C:34]4[O:35][C:36]([F:39])([F:38])[O:37][C:33]=4[CH:32]=3)[CH2:30][CH2:29]2)=[O:27])[CH:22]=[CH:21][C:20]=1[CH3:42]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:39][C:36]1([F:38])[O:35][C:34]2[CH:40]=[CH:41][C:31]([C:28]3([C:26]([NH:25][C:23]4[CH:22]=[CH:21][C:20]([CH3:42])=[C:19]([C:6]5[CH:5]=[CH:4][C:3](=[O:17])[N:2]([CH3:1])[CH:7]=5)[N:24]=4)=[O:27])[CH2:30][CH2:29]3)=[CH:32][C:33]=2[O:37]1

Participants

6

Reactant 2

HCID 454801941-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-oneHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide

Product 1

HCID 68738797HCID 68738797, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (68 mg, 0.30 mmol), N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (88 mg, 0.24 mmol) in DME (1.5 mL) and 2 M Na2CO3 (0.24 mL) was added Pd(PPh3)4 (14 mg, 0.0030 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The mixture was partitioned between ethyl acetate and H2O before the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine and dried over MgSO4. After the removal solvent, the residue was purified by column chromatography (10-20% EtOAc-Hexane) to afford 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide (67 mg, 72%). 1H-NMR (400 MHz, CDCl3) δ 8.06 (d, J=8.4 Hz, 1H), 7.63 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.53-7.48 (m, 2H), 7.24 (td, J=10.0, 1.7 Hz, 2H), 7.12 (d, J=8.2 Hz, 1H), 6.61 (d, J=9.2 Hz, 1H), 3.60 (s, 3H), 2.33 (s, 3H), 1.77 (q, J=3.6 Hz, 2H), 1.19 (q, J=3.6 Hz, 2H). MS (ESI) m/e (M+H+) 440.2.

Workup

  1. customThe mixture was partitioned between ethyl acetate and H2O before the aqueous layer
  2. extractionwas extracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customAfter the removal solvent, the residue was purified by column chromatography (10-20% EtOAc-Hexane)

Sources & evidence

ORD record
ord-4bc3d03de6884ccda01ec2e9ef1810b1
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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