N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide → HCID 59165990, compound

HRID 2420924Notes

Reaction equation

HRID 2420924 reaction equation
[CH3:1][C:2]1([CH3:24])[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:10]=2)[CH2:4][O:3]1.Cl[C:26]1[N:31]=[C:30]([NH:32][C:33]([C:35]2([C:38]3[CH:48]=[CH:47][C:41]4[O:42][C:43]([F:46])([F:45])[O:44][C:40]=4[CH:39]=3)[CH2:37][CH2:36]2)=[O:34])[CH:29]=[CH:28][C:27]=1[CH3:49]>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:46][C:43]1([F:45])[O:42][C:41]2[CH:47]=[CH:48][C:38]([C:35]3([C:33]([NH:32][C:30]4[CH:29]=[CH:28][C:27]([CH3:49])=[C:26]([C:12]5[CH:11]=[CH:10][C:9]([O:8][CH2:7][C@@H:5]6[CH2:4][O:3][C:2]([CH3:1])([CH3:24])[O:6]6)=[CH:14][CH:13]=5)[N:31]=4)=[O:34])[CH2:37][CH2:36]3)=[CH:39][C:40]=2[O:44]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 59165849HCID 59165849, compound

Product 1

HCID 59165990HCID 59165990, compoundYield 79%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a mixture of (R)-2-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (200 mg, 0.600 mmol) and N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (183 mg, 0.500 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 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 and dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography to yield (R)-1-(2,2-difluorobenzo [d][1,3]dioxol-5-yl)-N-(6-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-5-methylpyridin-2-yl)cyclopropanecarboxamide (212 mg, 79%). MS (ESI) m/e (M+H+) 539.2.

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-8afa0324167142a0b95cd7a228fa7024
Source dataset
uspto-grants-2011_06
Patent number
US07956052B2

Reaction notes

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