Tetrahydrofuran → (2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imidazol-5-yl)methanol

HRID 2068287노트

반응식

HRID 2068287 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[C:5]2I.[NH2:20][C:21]1[N:25]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:24]2[CH:32]=[CH:33][C:34]([CH2:36][OH:37])=[CH:35][C:23]=2[N:22]=1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCCC1>C(OCC)(=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[C:5]2[NH:20][C:21]1[N:25]([CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)[C:24]2[CH:32]=[CH:33][C:34]([CH2:36][OH:37])=[CH:35][C:23]=2[N:22]=1

참가 물질

8

반응물 5

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 583172565-Bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazoleHCID 67252967(2-Amino-1-cyclohexyl-1H-benzimidazol-5-yl)methanol

생성물 1

HCID 67255070(2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imidazol-5-yl)methanol수율 44.7%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8857Ethyl Acetate용매

실험 절차

In a 20 mL microwave reaction tube was weighed 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (653 mg, 0.00144 mol). To this was added (2-amino-1-cyclohexyl-1H-benzoimidazol-5-yl)methanol (322.1 mg, 0.001313 mol), trans-N1,N2-dimethylcyclohexane-1,2-diamine (121 mg, 0.000851 mol), copper(I) iodide (78 mg, 0.00041 mol) and potassium phosphate (554 mg, 0.00261 mol). The tube was purged with argon and tetrahydrofuran (14 mL, 0.17 mol) was then added. The reaction mixture was stirred for several minutes with argon sparging at room temp. The reaction mixture was then heated under microwave irradiation for 5 hours at 140° C. The reaction mixture was cooled and diluted with ethyl acetate and washed twice with aqueous sodium bicarbonate, once with dilute HCl and one final wash with dilute sodium bicarbonate. The organic phase was dried over sodium sulfate and concentrated. The residue (750 mg) was purified by flash chromatography using a 120 g silica gel cartridge and hexane and ethyl acetate eluent. The product was loaded onto the column with methylene chloride and the eluent was initially 10% ethyl acetate for 2 minutes then a gradient to 60% ethyl acetate over 20 mins. The product fractions were combined and concentrated to yield 334.6 mg of a pale greenish white solid.

후처리

  1. customIn a 20 mL microwave reaction tube was weighed
  2. additionwas then added
  3. temperatureThe reaction mixture was then heated under microwave irradiation for 5 hours at 140° C
  4. temperatureThe reaction mixture was cooled
  5. washwashed twice with aqueous sodium bicarbonate, once with dilute HCl and one
  6. washfinal wash with dilute sodium bicarbonate
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue (750 mg) was purified by flash chromatography
  10. customfor 2 minutes
  11. concentrationconcentrated

출처 및 근거

ORD 기록
ord-3ed89cef503f42b09b1105db0b89989d
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293923B2

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