Methane → 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-2,3-dihydro-1H-1,3-benzodiazol-2-one

HRID 1398510노트

반응식

HRID 1398510 반응식
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14](Br)[CH:15]=[CH:16][C:11]=3[NH:10][C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.C.[S:20]1[CH:24]=[CH:23][N:22]=[C:21]1[C:25]([OH:29])([C:27]#[CH:28])[CH3:26].N1CCCCC1>CCOC(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.[Cu]I>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([C:28]#[C:27][C:25]([OH:29])([C:21]4[S:20][CH:24]=[CH:23][N:22]=4)[CH3:26])[CH:15]=[CH:16][C:11]=3[NH:10][C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1

참가 물질

8

반응물 4

HCID 297MethaneHCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 681820071-(2-aminopyrimidin-4-yl)-6-bromo-2,3-dihydro-1H-1,3-benzodiazol-2-one

생성물 1

HCID 601640701-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(1,3-thiazol-2-yl)but-1-yn-1-yl]-2,3-dihydro-1H-1,3-benzodiazol-2-one

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1-(2-aminopyrimidin-4-yl)-6-bromo-2,3-dihydro-1H-1,3-benzodiazol-2-one (230 mg, 0.751 mmol) in EtOAc was added charcoal (5 mol %). The mixture was stirred at RT for 20 min then filtered and concentrated in vacuo. To the residue in a sealed tube was added 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (230 mg, 1.50 mmol), piperidine (2 mL), tetrakis(triphenylphosphine)palladium (43.4 mg, 0.038 mmol) and copper(I) iodide (14.3 mg, 0.075 mmol). The reaction mixture was then heated at 75° C. for 18 hr then partitioned between EtOAc (15 mL) and water (2 mL). The organic layer was concentrated in vacuo and the residue purified by reverse phase preparative HPLC to afford the title compound: 1H NMR (500 MHz, DMSO) δ 1.90 (3 H, s), 6.92 (2H, s), 6.95 (1H, s), 7.04 (1H, d, J=8.04 Hz), 7.21 (1H, dd, J=8.04, 1.42 Hz), 7.40 (1H, d, J=5.52 Hz), 7.68 (1H, d, J=3.31 Hz), 7.77 (1H, d, J=3.15 Hz), 8.26-8.36 (2H, m), 11.57 (1H, br. s.); LC-MS: m/z=+379.0 (M+H)+.

후처리

  1. filtrationthen filtered
  2. concentrationconcentrated in vacuo
  3. temperatureThe reaction mixture was then heated at 75° C. for 18 hr
  4. customthen partitioned between EtOAc (15 mL) and water (2 mL)
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe residue purified by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-f865451a239f4ca9828bbcc581a94402
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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