Potassium Iodide → 4'-{5-[(2-Hydroxy-1-hydroxymethyl-ethylamino)-methyl]-[1,3,4]oxadiazol-2-yl}-6-methyl-biphenyl-3-carboxylic acid cyclopropylamide

HRID 31446

반응식

HRID 31446 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.[NH2:15][CH:16]([CH2:19][OH:20])[CH2:17][OH:18].[I-].[K+].[CH:23]1([NH:26][C:27](=[O:44])[C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.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:23]1([NH:26][C:27]([C:28]2[CH:33]=[C:32]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[O:4][C:3]([CH2:2][NH:15][CH:16]([CH2:19][OH:20])[CH2:17][OH:18])=[N:7][N:6]=4)=[CH:9][CH:10]=3)[C:31]([CH3:34])=[CH:30][CH:29]=2)=[O:44])[CH2:24][CH2:25]1

참가 물질

8

반응물 5

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 68294SerinolHCID 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 100708654'-{5-[(2-Hydroxy-1-hydroxymethyl-ethylamino)-methyl]-[1,3,4]oxadiazol-2-yl}-6-methyl-biphenyl-3-carboxylic acid cyclopropylamide

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
20 °C

실험 절차

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole (Intermediate 7) (48 mg, 0.15 mmol), serinol (206 mg, 2.25 mmol) and potassium iodide (25 mg, 0.15 mmol) were dissolved in dimethylformamide (1 ml) and stirred for 18 hours at 20° C. The reaction was evaporated to dryness in vacuo and the product was flushed through a 10 g silica SPE cartridge, eluting with 95:5 ethyl acetate:methanol, to remove inorganic material. Without further purification the crude product was dissolved in 1,2 dimethoxyethane (4 ml). 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) were added. The reaction was heated under nitrogen at 80° C. for 18 hours. Solvent was removed in vacuo and the residue was purified by mass-directed HPLC to yield the desired product.

후처리

  1. customThe reaction was evaporated to dryness in vacuo
  2. customthe product was flushed through a 10 g silica SPE cartridge
  3. washeluting with 95:5 ethyl acetate
  4. custommethanol, to remove inorganic material
  5. customWithout further purification the crude product
  6. dissolutionwas dissolved in 1,2 dimethoxyethane (4 ml)
  7. temperatureThe reaction was heated under nitrogen at 80° C. for 18 hours
  8. customSolvent was removed in vacuo
  9. customthe residue was purified by mass-directed HPLC

출처 및 근거

ORD 기록
ord-ada3c6ed74304513bd5f7a6122521efc
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425555B2

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