Cesium carbonate → 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide

HRID 1428602노트

반응식

HRID 1428602 반응식
[CH3:1][N:2]([CH3:36])[CH2:3][CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([NH:12][C:13](=[O:31])[CH2:14][C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][C:16]=2[F:30])=[CH:8][C:7]=1[C:32]([F:35])([F:34])[F:33].[CH2:37]([O:44][C:45]1[CH:50]=[C:49]([O:51][CH2:52][CH3:53])[C:48](I)=[CH:47][N:46]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:37]([O:44][C:45]1[N:46]=[CH:47][C:48]([C:18]2[CH:19]=[CH:20][C:15]([CH2:14][C:13]([NH:12][C:9]3[CH:10]=[N:11][C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:36])=[C:7]([C:32]([F:33])([F:34])[F:35])[CH:8]=3)=[O:31])=[C:16]([F:30])[CH:17]=2)=[C:49]([O:51][CH2:52][CH3:53])[CH:50]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 90415933N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamideHCID 904176602-(Benzyloxy)-4-ethoxy-5-iodopyridine

생성물 1

HCID 904155782-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide수율 11.9%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A solution of N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (30 mg, 0.059 mmol), 2-(benzyloxy)-4-ethoxy-5-iodopyridine (20.84 mg, 0.059 mmol), PdCl2(dppf) (42.9 mg, 0.059 mmol) and Cs2CO3 (19.12 mg, 0.059 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was stirred at 110° C. for 15 min. After LCMS analysis showed the starting material had disappeared, the solvent was removed in vacuo. The residue was dissolved in EA (30 mL) and washed with H2O (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC (DCM/MeOH=10/1) to yield 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-2-fluorophenyl)-N-(6-(2-(dimethylamino)ethoxy)-5-(trifluoromethyl)pyridin-3-yl)acetamide (5 mg, 6.97 μmol, 11.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.56 (s, 1H), 8.33 (d, J=2.0 Hz, 1H), 7.99 (s, 1H), 7.48-7.30 (m, 8H), 6.51 (s, 1H), 5.38 (s, 2H), 4.64 (t, J=5.2 Hz, 2H), 4.16 (m, 2H), 3.84 (s, 2H), 3.03 (t, J=5.2 Hz, 2H), 2.53 (s, 6H), 1.40 (t, J=7.0 Hz, 3H); ES-LCMS m/z 613.1 (M+H).

후처리

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in EA (30 mL)
  3. washwashed with H2O (10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative TLC (DCM/MeOH=10/1)

출처 및 근거

ORD 기록
ord-78e88a4caa154ae891e9b177cd3c7e4e
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08937071B2

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