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

HRID 2409531노트

반응식

HRID 2409531 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].[C:21]([C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1)#[N:22].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:26]4[CH:27]=[CH:28][C:23]([C:21]#[N:22])=[N:24][CH:25]=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 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 667169392-(3,4-Dimethoxy-phenyl)-5-iodo-6-methyl-imidazo[2,1-b][1,3,4]thiadiazole

생성물 1

HCID 469136315-[2-(3,4-Dimethoxy-phenyl)-6-methyl-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-pyridine-2-carbonitrile수율 2%

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), 2-cyanopyridine-5-boronic acid pinacol ester (0.095 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% DCM in hexane, then 0-3% MeOH in DCM). Product fractions were concentrated to give a solid that was further purified by preparative HPLC affording the pure product (0.002 g, 2% yield). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min): tR=5.52 min, [M+H]+ m/z 378.1. 1H NMR (300 MHz, CDCl3) δ/ppm 9.16 (d, J=1.5, 1H), 8.18 (dd, J=8.4, 2.2, 1H), 7.82-7.67 (m, 1H), 7.41-7.28 (m, 2H), 6.89 (d, J=8.4, 0H), 3.91 (s, 3 H), 3.89 (s, 3 H), 2.54 (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% DCM in hexane
  7. concentrationProduct fractions were concentrated
  8. customto give a solid
  9. customthat was further purified by preparative HPLC

출처 및 근거

ORD 기록
ord-1a4a030bc7c14432b57df06e5f2a5c54
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815918B2

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