HOAt → HCID 11115267, compound

HRID 896928Notes

Reaction equation

HRID 896928 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][C:21]([CH3:29])([CH3:28])[CH2:22]/[CH:23]=[CH:24]/[C:25]([OH:27])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH2:40]([C@@H:47]([N:59]([CH3:76])[C:60](=[O:75])[C@H:61]([NH:73][CH3:74])[CH2:62][C:63]1[CH:72]=[CH:71][C:70]2[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=2)[CH:64]=1)[C:48]([N:50]1[CH2:54][CH2:53][CH2:52][C@H:51]1[CH2:55][N:56]([CH3:58])[CH3:57])=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>ClCCl.CN(C)C=O.C(N(C(C)C)C(C)C)C.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C:21]([CH3:29])([CH3:28])[CH2:22]/[CH:23]=[CH:24]/[C:25](=[O:27])[N:73]([C@@H:61]([C:60](=[O:75])[N:59]([C@H:47]([CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:48]([N:50]1[CH2:54][CH2:53][CH2:52][C@H:51]1[CH2:55][N:56]([CH3:57])[CH3:58])=[O:49])[CH3:76])[CH2:62][C:63]1[CH:72]=[CH:71][C:70]2[C:65](=[CH:66][CH:67]=[CH:68][CH:69]=2)[CH:64]=1)[CH3:74])([CH3:14])([CH3:15])[CH3:16]

Participants

9

Reactant 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 10940042HCID 10940042, compound

Product 1

HCID 11115267HCID 11115267, compoundYield 98%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (132 mg, 0.69 mmol) was added to a solution of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (168 mg, 0.69 mmol) and 1-hydroxy-7-azabenzotriazole (94 mg, 0.69 mmol) in dichloromethane (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-N-[(1R)-1-benzyl-2-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide (345 mg, 0.69 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml) and ethyldiisopropylamine were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (70 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml). The aqueous phase was extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 491 mg of {(3E)-4-[N-((1R)-1-{N-[(1R)-1-benzyl-2-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (70 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×50 ml)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customThe crude product was purified by flash chromatography on silica (40 g)

Sources & evidence

ORD record
ord-1b2f72ec424d4906b551ab3837e2e12c
Source dataset
uspto-grants-2005_07
Patent number
US06919315B1

Reaction notes

Loading…