Cesium carbonate → 2-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide

HRID 1472549

반응식

HRID 1472549 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH3:21][N:22]1[C:26]([CH3:27])=[C:25]([NH2:28])[CH:24]=[N:23]1.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.C1COCC1>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:28][C:25]2[CH:24]=[N:23][N:22]([CH3:21])[C:26]=2[CH3:27])=[N:3][CH:4]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 5738131,5-dimethyl-1H-pyrazol-4-amineHCID 634876Binap, (A+-)-HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

생성물 1

HCID 462150972-({5-Chloro-2-[(1,5-dimethyl-1H-pyrazol-4-yl)amino]-4-pyridinyl}amino)-N-(methyloxy)benzamide수율 7.3%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 22018518Dioxane tetrahydrofuran용매

반응 조건

온도
150 °C

실험 절차

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (200 mg, 0.64 mmol), 1,5-dimethyl-1H-pyrazol-4-amine (142 mg, 1.28 mmol), cesium carbonate (626 mg, 1.92 mmol) and dioxane/THF (3:1 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (5.8 mg, 0.03 mmol) and BINAP (40 mg, 0.06 mmol) were added. The tube was sealed and the mixture was stirred in an oil bath at 150° C. overnight. The dark brown solution was filtered thru celite and evaporated. It was dissolved in MeOH and filtered thru an Acrodisc (Pall Corporation; www.pall.com) and further purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). The dark brown oil residue was dissolved in DMF and water was slowly added. A tan precipitate crashed out and was filtered off and dried under vacuum at 40° C. for 2 hrs to afford the desired product (18 mg, 7.3%) as a tan solid. LC-MS [M+H]+=387.1, 389.1. 1H NMR (400 MHz, DMSO-d6) d ppm 11.91 (br. s., 1 H) 9.41 (br. s., 1 H) 7.85-7.98 (m, 2 H) 7.49-7.59 (m, 3 H) 7.42 (br. s., 1 H) 7.07-7.13 (m, 1 H) 6.50 (br. s., 1 H) 3.69 (d, J=10.36 Hz, 6 H) 2.11 (s, 3 H).

후처리

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customThe tube was sealed
  3. filtrationThe dark brown solution was filtered thru celite
  4. customevaporated
  5. dissolutionIt was dissolved in MeOH
  6. filtrationfiltered
  7. customfurther purified on preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid)
  8. dissolutionThe dark brown oil residue was dissolved in DMF
  9. additionwater was slowly added
  10. filtrationwas filtered off
  11. customdried under vacuum at 40° C. for 2 hrs

출처 및 근거

ORD 기록
ord-dde0a3e7dd9441daa8855824aded77eb
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012479B2

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