Triethylamine → 6-Fluoro-2,4,8,19,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene

HRID 541857노트

반응식

HRID 541857 반응식
Cl.Cl.[NH2:3][C:4]1[CH:9]=[C:8]([CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([NH:18][C:19]3[C:24]([F:25])=[CH:23][N:22]=[C:21](Cl)[N:20]=3)[CH:15]=[CH:16][CH:17]=2)[CH:7]=[CH:6][N:5]=1.C(N(CC)CC)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O.O1CCOCC1>[F:25][C:24]1[CH:23]=[N:22][C:21]2[NH:3][C:4]3[N:5]=[CH:6][CH:7]=[C:8]([CH:9]=3)[CH2:10][CH2:11][C:12]3[CH:13]=[C:14]([NH:18][C:19]=1[N:20]=2)[CH:15]=[CH:16][CH:17]=3

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86636273N-{3-[2-(2-Aminopyridin-4-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine Dihydrochloride

생성물 1

HCID 579617686-Fluoro-2,4,8,19,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene수율 30.2%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

실험 절차

To a mixture of N-{3-[2-(2-aminopyridin-4-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine dihydrochloride (35.0 mg, 0.084 mmol) and triethylamine (0.035 mL, 0.25 mmol) in a mixed solvent of 1,4-dioxane (0.70 mL) and N,N-dimethylformamide (0.70 mL) were added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.8 mg, 0.01 mmol), palladium acetate (2.3 mg, 0.01 mmol) and cesium carbonate (54.7 mg, 0.17 mmol). The mixture was degassed by bubbling N2 through the solution. The sealed tube was then microwaved at 160° C. for 30 min. The reaction mixture was diluted with THF/MeOH, filtered and concentrated to give the residue, which was purified by silica gel column chromatography to provide the desired product as a white powder (7.8 mg, 30%). LCMS for C17H15FN5 (M+H)+: m/z=308.1. 1H NMR (400 MHz, CD3OD): δ 8.09 (d, J=5.2 Hz, 1H), 8.00 (s, 1H), 7.96 (d, J=4.0 Hz, 1H), 7.81 (d, J=1.6 Hz, 1H), 7.31 (m, 1H), 7.04 (m, 2H), 6.91 (m, 1H).

후처리

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. customThe sealed tube was then microwaved at 160° C. for 30 min
  4. additionThe reaction mixture was diluted with THF/MeOH
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue, which
  8. customwas purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-a59d687c970a44f8b56ffd992648c1b1
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871753B2

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