Dicyclohexylcarbodiimide → HCID 53654747, compound

HRID 1938606Notes

Reaction equation

HRID 1938606 reaction equation
[OH:1][CH:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[NH:10]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[CH:39]=[CH:38][C:24]3[N:25]([CH:28]([CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:29](O)=[O:30])[CH:26]=[N:27][C:23]=3[CH:22]=2)=[N:13][N:12]=[N:11]1.C(N(CC)C(C)C)(C)C.OC1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C>[O:30]=[C:29]([N:5]1[CH2:6][CH:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])[CH:28]([N:25]1[C:24]2[CH:38]=[CH:39][C:21]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[C:14]3[N:10]=[N:11][NH:12][N:13]=3)=[CH:22][C:23]=2[N:27]=[CH:26]1)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 69248L-Proline, 4-hydroxy-, cis-HCID 81531DiisopropylethylamineHCID 178418300HCID 178418300, compoundHCID 178443861HCID 178443861, compound

Product 1

HCID 53654747HCID 53654747, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-Hydroxy-L-proline lacetone hydrobromide (0.74 mmoles, 143 mg) and 2-[5-(2-tetrazol-5-ylphenyl)benzimidazol-1-yl]octanoic acid (0.74 mmoles, 300 mg) were dissolved in 30 ml DMF and cooled to 0° C. N,N-Diisopropylethylamine (0.74 moles, 0.15 ml) was added. The solution was stirred for 10 minutes. Hydroxybenzotriazole (0.74 mmoles, 100 mg) and then dicyciohexylcarbodiimide (0.74 mmoles, 153 mg) were added. The solution was stirred at room temperature for 3 days. The intermediate was extracted in ethyl acetate. The ethyl acetate solution was washed with water, dried over sodium sulfate, concentrated. The residue was chromatographed over silica gel eluted with 10% methanol in ethyl acetate. The reaction yielded 200 mg of 1-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazol-1-yl]octyl]-4-hydroxy-L-proline lacetone. (MS). The lactone was dissolved in 2.0 ml methanol/2.0 ml 2N NaOH and stirred at room temperature for 16 hours The solvent was removed in vacuo. Water was added. The solution was extracted with ether. The pH of the aqueous layer was adjusted to 3.2 using 2N HCl. The precipitate was filtered, washed with water, and dried to yield 37 mg. The aqueous phase was extracted with ethyl acetate, dried and concentrated to yield an additional 60 mg of 1-[1-oxo-2-[5-[2-(2H-tetrazol-5-yl)phenyl]-1H-benzimidazole-1-yl]octyl]-4-hydroxy-L -prolite. (MS)

Workup

  1. stirringThe solution was stirred at room temperature for 3 days
  2. extractionThe intermediate was extracted in ethyl acetate
  3. washThe ethyl acetate solution was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was chromatographed over silica gel
  7. washeluted with 10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-785be66b79334aedb2f3fe5558b0764d
Source dataset
uspto-grants-1997_12
Patent number
US05693633

Reaction notes

Loading…