Cesium carbonate → 2-{[5-Chloro-2-({1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-yl}amino)-4-pyridinyl]amino}-N-methylbenzamide

HRID 62500

반응식

HRID 62500 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[CH2:20]([N:22]1[C:26]([NH2:27])=[CH:25][C:24]([CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[N:23]1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[CH:7][C:2]([NH:27][C:26]2[N:22]([CH2:20][CH3:21])[N:23]=[C:24]([CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[CH:25]=2)=[N:3][CH:4]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 575168912-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamideHCID 575169001-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-amine

생성물 1

HCID 462150962-{[5-Chloro-2-({1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-yl}amino)-4-pyridinyl]amino}-N-methylbenzamide수율 39.2%

시약·촉매·용매 2

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

반응 조건

온도
170 °C

실험 절차

To a 5-mL microwave tube were added 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methylbenzamide (100 mg, 0.338 mmol), 1-ethyl-3-[2-(1-pyrrolidinyl)ethyl]-1H-pyrazol-5-amine (70.3 mg, 0.338 mmol), cesium carbonate (330 mg, 1.013 mmol), and 1,4-dioxane (2 mL), and the mixture was degassed by bubbling nitrogen through for 15 min. Palladium (II) acetate (3.79 mg, 0.017 mmol) and BINAP (21.03 mg, 0.034 mmol) were added, and the reaction mixture was heated at 170° C. with stirring under microwave conditions for 40 min. The reaction mixture was filtered and concentrated. The residue was purified by using RP-HPLC under basic conditions (Gemini 5u C18(2) 110A, AXI. 50×30.00 mm 5 micron: 7.3-minute run, 47 mL/min, 40% ACN/H2O, 0.1% NH4OH to 90% ACN/H2O, 0.1% NH4OH with UV detection at 254 nm) to give the title compound (62 mg). MS: (M+H)+=468.1. 1H NMR (400 MHz, DMSO-d6) ppm 1.21 (t, J=7.2 Hz, 3 H), 1.67 (m, 4H), 2.45 (m, 4), 2.60 (m, 4H), 2.77 (d, J=4.0 Hz, 3H), 3.89 (q, J=7.2 Hz, 2H), 6.03 (s, 1H), 6.74 (s, 1H), 7.11 (m, 1H), 7.49 (m, 1H), 7.54 (m, 1H), 7.71 (d, J=7.2 Hz, 1H), 8.00 (s, 1H).

후처리

  1. customthe mixture was degassed
  2. customby bubbling nitrogen through for 15 min
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. customThe residue was purified
  6. customunder basic conditions (Gemini 5u C18(2) 110A, AXI. 50×30.00 mm 5 micron: 7.3-minute run, 47 mL/min, 40% ACN/H2O, 0.1% NH4OH to 90% ACN/H2O, 0.1% NH4OH with UV detection at 254 nm)

출처 및 근거

ORD 기록
ord-84549fe95b914557b1362ccba6ef7dd5
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09446034B2

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