Dichloromethane → 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxyphenylamino)pyridin-2-yl)cyclopropanecarboxamide

HRID 1516902Notes

Reaction equation

HRID 1516902 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][CH:19]=[C:18](Br)[N:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(Cl)Cl.[CH3:68][O:69][C:70]1[CH:76]=[CH:75][CH:74]=[CH:73][C:71]=1[NH2:72]>C(N(CC)CC)C.O1CCOCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([NH:72][C:71]5[CH:73]=[CH:74][CH:75]=[CH:76][C:70]=5[O:69][CH3:68])[N:17]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 70002-MethoxyanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 591658951-(Benzo[d][1,3]dioxol-6-yl)-N-(6-bromopyridin-2-yl)cyclopropanecarboxamide

Product 1

HCID 578951231-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxyphenylamino)pyridin-2-yl)cyclopropanecarboxamide

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-bromopyridin-2-yl)cyclopropanecarboxamide (72 mg, 0.2 mmol), XANTPHOS (7.00 mg, 0.008 mmol), KtBuO (31 mg, 0.28 mmol), (DPPF)2PdCl2.CH2Cl2 (33.00 mg, 0.24 mmol), and 2-methoxyaniline (30 mg, 0.24 mmol), 1,4-dioxane (0.400 mL) and triethylamine (0.200 mL) were added. The reaction mixture was heated to 150° C. in a microwave reactor for 10 minutes. The resulting material was cooled to room temperature. The solvent was evaporated under reduced pressure. The resulting mixture was dissolved in dichloromethane and washed with H2O. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to yield 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methoxyphenylamino)pyridin-2-yl)cyclopropanecarboxamide which was then treated with HCl in MeOH to form the HCl salt (2.4 mg, 0.0055 mmol, 2.7%). ESI-MS m/z calc. 403.1, found 404.5 (M+1)+; retention time 3.01 minutes.

Workup

  1. temperatureThe resulting material was cooled to room temperature
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionThe resulting mixture was dissolved in dichloromethane
  4. washwashed with H2O
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. customevaporated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-5d47e1f08d2b41f9b39a8833238e5e6f
Source dataset
uspto-grants-2012_07
Patent number
US08227615B2

Reaction notes

Loading…