Sodium Carbonate → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 1442837Notes

Reaction equation

HRID 1442837 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][O:14][C:15]3=[O:18])=[CH:11][CH:10]=2)O1.Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]([C:30]2([C:33]3[CH:43]=[CH:42][C:36]4[O:37][C:38]([F:41])([F:40])[O:39][C:35]=4[CH:34]=3)[CH2:32][CH2:31]2)=[O:29])[CH:24]=[CH:23][C:22]=1[CH3:44].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.COCCOC>[F:41][C:38]1([F:40])[O:37][C:36]2[CH:42]=[CH:43][C:33]([C:30]3([C:28]([NH:27][C:25]4[CH:24]=[CH:23][C:22]([CH3:44])=[C:21]([C:9]5[CH:17]=[C:16]6[C:12](=[CH:11][CH:10]=5)[CH2:13][O:14][C:15]6=[O:18])[N:26]=4)=[O:29])[CH2:32][CH2:31]3)=[CH:34][C:35]=2[O:39]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamideHCID 591659366-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1(3H)-isobenzofuranone

Product 1

HCID 591661131-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one (39 mg, 0.15 mmol), N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (37 mg, 0.10 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol) were placed in a microwave vial. DME (1 mL) and saturated aq. Na2CO3 (100 μL) were added and the reaction vial was flushed with N2 and sealed. The reaction was heated in the microwave at 120° C. for 20 minutes before it was partitioned between ethyl acetate and H2O. The organic layer was filtered and concentrated. The residue was dissolved in DMSO and purified by reverse-phase HPLC to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(3-oxo-1,3-dihydroisobenzofuran-5-yl)pyridin-2-yl)cyclopropanecarboxamide. ESI-MS m/z calc. 464.1, found 465.3 (M+1)+. Retention time 1.96 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.94-7.86 (m, 3H), 7.76-7.73 (m, 2H), 7.56 (d, J=1.5 Hz, 1H), 7.41-7.33 (m, 2H), 5.47 (s, 2H), 2.26 (s, 3H), 1.53-1.50 (m, 2H), 1.19-1.16 (m, 2H).

Workup

  1. customthe reaction
  2. customvial was flushed with N2
  3. customsealed
  4. customwas partitioned between ethyl acetate and H2O
  5. filtrationThe organic layer was filtered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DMSO
  8. custompurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-e1cc49ba7d0947f9bd7afaed4cd4c18f
Source dataset
uspto-grants-2010_02
Patent number
US07659268B2

Reaction notes

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