1,2-Dichloroethane → HCID 178448272、化合物

HRID 847302

反応式

HRID 847302 の反応式
[NH2:1][C@@H:2]([CH2:42][C:43]1[N:44]=[CH:45][NH:46][CH:47]=1)[C:3]([NH:5][C@@H:6]([CH2:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[C@@H:7]([OH:34])[CH2:8][C@@H:9]([CH:31]([CH3:33])[CH3:32])[CH:10]([OH:30])[CH2:11][N:12]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:4].[NH:48](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:49]([C:57](O)=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(N1CCOCC1)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C=O>[CH:36]1([CH2:35][C@H:6]([NH:5][C:3](=[O:4])[C@H:2]([CH2:42][C:43]2[N:44]=[CH:45][NH:46][CH:47]=2)[NH:1][C:57](=[O:58])[C@H:49]([CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[NH2:48])[C@@H:7]([OH:34])[CH2:8][C@@H:9]([CH:31]([CH3:33])[CH3:32])[CH:10]([OH:30])[CH2:11][N:12]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]1

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 978331Fmoc-phenylalanineHCID 178448273HCID 178448273、化合物

生成物 1

HCID 178448272HCID 178448272、化合物収率 67.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 340 mg (0.52 mmol) of benzyl [(2RS,3S, 5S,6S)-6-[(S)-α-amino-4-imidazolepropionamido]-7-cyclohexyl-2,5-dihydroxy-3-isopropylheptyl]-(2-pyridylmethyl)carbamate, 225 mg (0.58 mmol) of Fmoc-Phe-OH, 0.132 ml (1.05 mmol) of 4-ethylmorpholine, 155 mg (1.15 mmol) of HOBT, 121 mg (0.63 mmol) of EDC and 10 ml of dimethylformamide is stirred at room temperature overnight. Thereafter, the reaction mixture is poured into 70 ml of ice-cold 2N sodium bicarbonate solution and extracted three times with 150 ml of ethyl acetate each time. The organic extracts are washed in succession with 70 ml of sodium bicarbonate solution and 70 ml of saturated sodium chloride solution, combined, dried and evaporated. The residue (640 mg) in 30 ml of methylene chloride and 1 ml of piperidine is stirred at room temperature for 2.5 hours. Then, the reaction mixture is evaporated and the residue (500 mg) is chromatographed on 50 mg of silica gel with a 14:1:0.1 mixture of methylene chloride, methanol and ammonia as the eluting agent. Recrystallization of the crude product obtained (320 mg) from methylene chloride/ether/hexane yields 280 mg of benzyl [(2RS,3S,5S,6S)-7-cyclohexyl-2,5-dihydroxy-3-isopropyl-6-[[N-(3-phenyl-L-alanyl)-L-histidyl]amino]heptyl]-(2-pyridylmethyl)carbamate as a white solid, melting point 94°.

後処理

  1. extractionextracted three times with 150 ml of ethyl acetate each time
  2. washThe organic extracts are washed in succession with 70 ml of sodium bicarbonate solution and 70 ml of saturated sodium chloride solution
  3. customdried
  4. customevaporated
  5. stirringThe residue (640 mg) in 30 ml of methylene chloride and 1 ml of piperidine is stirred at room temperature for 2.5 hours
  6. customThen, the reaction mixture is evaporated
  7. customthe residue (500 mg) is chromatographed on 50 mg of silica gel with a 14:1:0.1 mixture of methylene chloride, methanol and ammonia as the eluting agent
  8. customRecrystallization of the crude product
  9. customobtained (320 mg) from methylene chloride/ether/hexane

出典と根拠

ORDレコード
ord-ce3e8fcd89e044c080778e484177ee43
出典データセット
uspto-grants-1992_08
特許番号
US05140011

関連ノート

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