Triethylamine → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide

HRID 869914Notes

Reaction equation

HRID 869914 reaction equation
[F:1][C:2]1([F:32])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([O:29]C)=[CH:27][CH:28]=5)[C:20]([CH3:31])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.C(N(CC)CC)C>O1CCOCC1.Cl>[F:32][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH3:31])=[C:21]([C:23]5[CH:28]=[CH:27][C:26](=[O:29])[NH:25][CH:24]=5)[N:22]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 687389231-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(6'-methoxy-3-methyl-2,3'-bipyridin-6-yl)cyclopropanecarboxamide

Product 1

HCID 251183661-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-n-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamideYield 40.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (482 mg, 1.10 mmol) was dissolved in a mixture of 6 mL of 1,4-dioxane and 3 mL of 4M aqueous hydrochloric acid. This solution was heated at 90° C. for 1.5 hours. The crude reaction mixture was quenched with one equivalent of triethylamine and then evaporated to dryness. The crude product was then partitioned between dichloromethane and water. The organic layer was separated, dried over sodium sulfate, and then purified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5-methyl-6-(6-oxo-1,6-dihydropyridin-3-yl)pyridin-2-yl)cyclopropanecarboxamide as a white solid (189 mg, 40%). ESI-MS m/z calc. 425.1. found 426.3 (M+1)+. Retention time 1.53 minutes. 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.91 (s, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.66-7.64 (m, 2H), 7.56-7.55 (m, 2H), 7.41 (d, J=8.3 Hz, 1H), 7.34 (dd, J=1.7, 8.3 Hz, 1H), 6.36 (d, J=9.5 Hz, 1H), 2.28 (s, 3H), 1.52-1.49 (m, 2H), 1.18-1.15 (m, 2H).

Workup

  1. customThe crude reaction mixture
  2. customevaporated to dryness
  3. customThe crude product was then partitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. custompurified on 12 g of silica gel utilizing a gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-152dbd55f5af43819aed9c368d915540
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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