N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide → HCID 59165878, compound

HRID 1442834Notes

Reaction equation

HRID 1442834 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].Cl[C:27]1[N:32]=[C:31]([NH:33][C:34]([C:36]2([C:39]3[CH:49]=[CH:48][C:42]4[O:43][C:44]([F:47])([F:46])[O:45][C:41]=4[CH:40]=3)[CH2:38][CH2:37]2)=[O:35])[CH:30]=[CH:29][C:28]=1[CH3:50]>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:47][C:44]1([F:46])[O:43][C:42]2[CH:48]=[CH:49][C:39]([C:36]3([C:34]([NH:33][C:31]4[CH:30]=[CH:29][C:28]([CH3:50])=[C:27]([C:11]5[CH:12]=[CH:13][CH:14]=[C:9]([C:3]([OH:8])([C:4]([F:6])([F:5])[F:7])[C:2]([F:1])([F:25])[F:24])[CH:10]=5)[N:32]=4)=[O:35])[CH2:38][CH2:37]3)=[CH:40][C:41]=2[O:45]1

Participants

6

Reactant 2

HCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamideHCID 59165806HCID 59165806, compound

Product 1

HCID 59165878HCID 59165878, compoundYield 80%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a mixture of 1,1,1,3,3,3-hexafluoro-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ol (50 mg, 0.13 mmol) and N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (37 mg, 0.10 mmol) in DME (1 mL) and 2 M Na2CO3 (0.1 mL) was added Pd(PPh3)4 (6 mg, 0.005 mmol). The mixture was heated in 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 (20-40% ethyl acetate-hexane) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(3-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-5-methylpyridin-2-yl)cyclopropane-carboxamide (44 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 8.01 (d; J=8.4 Hz, 1H), 7.71 (s, 1H), 7.66-7.62 (m, 2H), 7.53-7.43 (m, 3H), 7.15 (td, J=8.8, 1.7 Hz, 2H), 7.00 (d, J=8.2 Hz, 1H), 2.19 (s, 3H), 1.68 (q, J=3.6 Hz, 2H), 1.10 (q, J=3.6 Hz, 2H). MS (ESI) m/e (M+H+) 575.3.

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 (20-40% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-62bc88ddfd524403ab6ea5ae634a2246
Source dataset
uspto-grants-2010_02
Patent number
US07659268B2

Reaction notes

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