2-Methoxypyrimidine-5-boronic acid → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxypyrimidin-5-yl)-5-methylpyridin-2-yl)cyclopropanecarboxamide

HRID 1442832Notes

Reaction equation

HRID 1442832 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][N:4]=1.Cl[C:13]1[N:18]=[C:17]([NH:19][C:20]([C:22]2([C:25]3[CH:35]=[CH:34][C:28]4[O:29][C:30]([F:33])([F:32])[O:31][C:27]=4[CH:26]=3)[CH2:24][CH2:23]2)=[O:21])[CH:16]=[CH:15][C:14]=1[CH3:36]>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:33][C:30]1([F:32])[O:29][C:28]2[CH:34]=[CH:35][C:25]([C:22]3([C:20]([NH:19][C:17]4[CH:16]=[CH:15][C:14]([CH3:36])=[C:13]([C:6]5[CH:5]=[N:4][C:3]([O:2][CH3:1])=[N:8][CH:7]=5)[N:18]=4)=[O:21])[CH2:24][CH2:23]3)=[CH:26][C:27]=2[O:31]1

Participants

6

Reactant 2

HCID 27367782-Methoxypyrimidine-5-boronic acidHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide

Product 1

HCID 591658501-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxypyrimidin-5-yl)-5-methylpyridin-2-yl)cyclopropanecarboxamideYield 64%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a mixture of 2-methoxypyrimidin-5-ylboronic acid (92 mg, 0.60 mmol) and N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-carboxamide (180 mg, 0.50 mmol) in DME (3 mL) and 2 M Na2CO3 (1 mL) was added Pd(PPh3)4 (29 mg, 0.025 mmol). The mixture was heated in a microwave oven at 120° C. for 30 min. The mixture was partitioned between ethyl acetate and H2O and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxypyrimidin-5-yl)-5-methylpyridin-2-yl)cyclopropanecarboxamide (140 mg, 64%). 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 2H), 8.03 (d, J=8.4 Hz, 1H), 7.58 (s, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.18 (dd, J=8.6, 2.1 Hz, 1H), 7.13 (d, J=1.6 Hz, 1H), 7.04 (d, J=8.2 Hz, 1H), 3.98 (s, 3H), 2.26 (s, 3H), 1.68 (q, J=3.6 Hz, 2H), 1.12 (q, J=3.6 Hz, 2H). MS (ESI) m/e (M+H+) 441.3.

Workup

  1. customThe mixture was partitioned between ethyl acetate and H2O
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8c88e46b968d439b931cc8cf275cd6fb
Source dataset
uspto-grants-2010_02
Patent number
US07659268B2

Reaction notes

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