Potassium Iodide → 6-Methyl-4'-(5-methylaminomethyl-[1,3,4]oxadiazol-2-yl)biphenyl-3-carboxylic acid cyclopropylamide

HRID 31444

반응식

HRID 31444 반응식
Cl[CH2:2][C:3]1[O:4][C:5]([C:8]2[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=2)=[N:6][N:7]=1.[I-].[K+].[CH:17]1([NH:20][C:21](=[O:38])[C:22]2[CH:27]=[CH:26][C:25]([CH3:28])=[C:24](B3OC(C)(C)C(C)(C)O3)[CH:23]=2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:45][NH2:46]>O1CCCC1.COCCOC.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>[CH:17]1([NH:20][C:21]([C:22]2[CH:27]=[C:26]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[O:4][C:3]([CH2:2][NH:46][CH3:45])=[N:7][N:6]=4)=[CH:9][CH:10]=3)[C:25]([CH3:28])=[CH:24][CH:23]=2)=[O:38])[CH2:19][CH2:18]1

참가 물질

9

반응물 5

HCID 4875Potassium IodideHCID 6329MethylamineHCID 10340Sodium CarbonateHCID 70910682-(Chloromethyl)-5-(4-iodophenyl)-1,3,4-oxadiazole2회HCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2회

생성물 1

HCID 100672106-Methyl-4'-(5-methylaminomethyl-[1,3,4]oxadiazol-2-yl)biphenyl-3-carboxylic acid cyclopropylamide

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
20 °C

실험 절차

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole (Intermediate 7) (48 mg, 0.15 mmol) and potassium iodide (25 mg, 0.15 mmol) were dissolved in 2M methylamine in tetrahydrofuran (2 ml) and stirred for 18 hours at 20° C. The reaction was evaporated to dryness in vacuo and the product was purified on a 10 g silica SPE cartridge (stepped solvent gradient 80:20 ethyl acetate:cyclohexane, 100% ethyl acetate, 95:5 ethyl acetate:methanol). The resulting material was dissolved in 1,2 dimethoxyethane (4 ml) with tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 17) (0.15 mmol) and 1M aqueous sodium carbonate (0.15 ml, 0.15 mmol). The reaction was heated under nitrogen at 80° C. for 18 hours. The solvent was removed in vacuo and the residue was purified by silica biotage chromatography eluting with 95:5 ethyl acetate:methanol.

후처리

  1. customThe reaction was evaporated to dryness in vacuo
  2. customthe product was purified on a 10 g silica SPE cartridge (stepped solvent gradient 80:20 ethyl acetate:cyclohexane, 100% ethyl acetate, 95:5 ethyl acetate:methanol)
  3. temperatureThe reaction was heated under nitrogen at 80° C. for 18 hours
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by silica biotage chromatography
  6. washeluting with 95:5 ethyl acetate

출처 및 근거

ORD 기록
ord-0bec7302b4ac43c28a46178bb4f7bc24
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425555B2

연결된 노트

불러오는 중…