Dichloromethane → 5-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine

HRID 2409532노트

반응식

HRID 2409532 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[C:32]([NH2:35])=[N:33][CH:34]=2)O1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.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]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][C:17]([CH3:20])=[C:18]([C:29]4[CH:30]=[C:31]([C:36]([F:39])([F:38])[F:37])[C:32]([NH2:35])=[N:33][CH:34]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 468641035-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amineHCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

생성물 1

HCID 469409475-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine수율 52%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole (0.125 g, 0.312 mmol, 1 eq), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (0.119 g, 0.414 mmol, 1.33 eq), Pd(dppf)Cl2.DCM (0.008 g, 0.009 mmol, 0.03 eq) and cesium carbonate (0.305 g, 0.935 mmol, 3 eq) in DME (4 mL) and water (0.1 mL) was heated in the microwave oven (45 min, 130° C.), cooled to RT, diluted with water, extracted with EtOAc and washed with brine. The organic layers were dried (MgSO4), filtered and concentrated, and the residue was purified by silica gel chromatography (0-100% EtOAc in hexane). Product fractions were concentrated and triturated with Et2O, the solid was filtered off and dried to give the desired product (solid, 0.070 g, 52%). HPLC-MS: (50-100% B in 8 min, 0.8 mL/min): tR=1.11 min, [M+H]+ m/z 436.0. 1H NMR (300 MHz, CDCl3) δ/ppm 8.62 (d, J=1.6, 1H), 8.22 (d, J=1.6, 0H), 7.44 (d, J=2.2, 1H), 7.39 (dd, J=8.2, 2.2, 1H), 6.96 (d, J=8.5, 1H), 5.11 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 2.53 (s, 1H).

후처리

  1. extractionextracted with EtOAc
  2. washwashed with brine
  3. dry with materialThe organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (0-100% EtOAc in hexane)
  7. concentrationProduct fractions were concentrated
  8. customtriturated with Et2O
  9. filtrationthe solid was filtered off
  10. customdried

출처 및 근거

ORD 기록
ord-50585fb1ecff44d8bd6a6964917819d6
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815918B2

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