Potassium Carbonate → (+/-)-2-{4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl}-5-chloro-indole-1-carboxylic acid tert-butyl ester

HRID 1433010노트

반응식

HRID 1433010 반응식
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][NH:9][CH2:8][C:7](=[O:11])[N:6]1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[C:15]([N:21]=[C:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:14]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[C:41]([O:45][C:46]([N:48]1[C:56]2[C:51](=[CH:52][C:53]([Cl:57])=[CH:54][CH:55]=2)[CH:50]=[C:49]1[CH2:58]Br)=[O:47])([CH3:44])([CH3:43])[CH3:42]>CC#N.C(OCC)C.O>[C:41]([O:45][C:46]([N:48]1[C:56]2[C:51](=[CH:52][C:53]([Cl:57])=[CH:54][CH:55]=2)[CH:50]=[C:49]1[CH2:58][N:9]1[CH2:8][C:7](=[O:11])[N:6]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[C:15]([N:21]=[C:22]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:14]=2)[CH:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:10]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 217084992-Bromomethyl-1-tert-butoxycarbonyl-5-chloroindoleHCID 54153171(+/-)-1-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-6-oxo-piperazine-2-carboxylic acid methyl ester

생성물 1

HCID 86760983(+/-)-2-{4-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl}-5-chloro-indole-1-carboxylic acid tert-butyl ester수율 55.2%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 21584184Diethylether water용매

실험 절차

To a mixture of (±)-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-6-oxo-piperazine-2-carboxylic acid methyl ester (630 mg, 1.39 mmol) and K2CO3 (380 mg, 2.78 mmol) in anhydrous CH3CN (5 mL) at 0° C. is added 2-bromomethyl-5-chloro-indole-1-carboxylic acid tert-butyl ester (720 mg, 2.09 mmol), EXAMPLE 21, in CH3CN (4 mL). The reaction mixture is allowed to warm to ambient temperature then maintained for 16 hours. The reaction mixture is diluted with diethyl ether/water and the layers are separated. The organic phase is washed twice with water, brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is chromatographed on silica (CH2Cl2 to 2% MeOH/CH2Cl2) to provide 550 mg (55%) of the title compound which is used directly in the next reaction without further characterization.

후처리

  1. temperaturethen maintained for 16 hours
  2. customthe layers are separated
  3. washThe organic phase is washed twice with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue is chromatographed on silica (CH2Cl2 to 2% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-03ca7cbe9bb447aa9a2c1ec0333e0ad6
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612075B2

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