1,2-Dichloroethane → HCID 178448272, compound

HRID 847302

Reaction equation

HRID 847302 reaction equation
[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

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 978331Fmoc-phenylalanineHCID 178448273HCID 178448273, compound

Product 1

HCID 178448272HCID 178448272, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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°.

Workup

  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

Sources & evidence

ORD record
ord-ce3e8fcd89e044c080778e484177ee43
Source dataset
uspto-grants-1992_08
Patent number
US05140011

Linked notes

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