Triethylamine → 6-Fluoro-2,4,8,17,22-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 541845노트

반응식

HRID 541845 반응식
Cl.Cl.[NH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([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: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+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:25][C:24]1[CH:23]=[N:22][C:21]2[NH:3][C:4]3[CH:9]=[CH:8][N:7]=[C:6]([CH:5]=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

7

반응물 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86636270N-{3-[2-(4-Aminopyridin-2-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine Dihydrochloride

생성물 1

HCID 579621426-Fluoro-2,4,8,17,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene수율 41%

시약·촉매·용매 2

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

실험 절차

To a mixture of N-{3-[2-(4-aminopyridin-2-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine dihydrochloride (50.0 mg, 0.12 mmol) and triethylamine (0.05 mL, 0.36 mmol) in dry 1,4-dioxane (1.0 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.16 mg, 0.007 mmol), palladium acetate (1.1 mg, 0.0048 mmol) and cesium carbonate (78.2 mg, 0.24 mmol). The cloudy mixture was degassed by bubbling N2 through the solution. The sealed tube was then microwaved at 150° C. for 30 min. The reaction mixture was diluted with THF, filtered and concentrated to give the residue, which was then triturated with MeOH/THF/EtOAc to provide the desired product as a white powder (15 mg, 41%). LCMS for C17H15FN5 (M+H)+: m/z=308.0. 1H NMR (400 MHz, DMSO-d6): δ 9.68 (s, 1H), 9.58 (s, 1H), 8.14 (m, 3H), 7.84 (s, 1H), 7.26 (dd, J=15.2, 7.2 Hz, 1H), 7.04 (dd, J=7.2, 2.0 Hz, 2H), 6.84 (dd, J=5.6, 2.0 Hz, 1H), 2.90 (m, 4H).

후처리

  1. customThe cloudy mixture was degassed
  2. customby bubbling N2 through the solution
  3. customThe sealed tube was then microwaved at 150° C. for 30 min
  4. additionThe reaction mixture was diluted with THF
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue, which
  8. customwas then triturated with MeOH/THF/EtOAc

출처 및 근거

ORD 기록
ord-30a3ede25652400c82b4a702fc21bdd1
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871753B2

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