Dichloromethane → HCID 10887168, compound

HRID 896921Notes

Reaction equation

HRID 896921 reaction equation
Cl.CN(C)[CH2:4][CH2:5][CH2:6]N=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].ON1[C:35]2N=[CH:37][CH:38]=[CH:39][C:34]=2N=N1.[CH2:40]([C@@H:47]([N:60]([CH3:77])[C:61](=[O:76])[C@@:62](C1C=CC2C(=CC=CC=2)C=1)([NH:64][CH3:65])[CH3:63])[C:48]([N:50]1[CH2:55][CH2:54][CH2:53][C@@H:52]([CH2:56][N:57]([CH3:59])[CH3:58])[CH2:51]1)=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.[CH2:78](N(C(C)C)C(C)C)[CH3:79].Cl[CH2:88]Cl>CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[NH:20][C:21]1([CH2:22]/[CH:23]=[CH:24]/[C:25](=[O:27])[N:64]([C@@H:62]([C:61](=[O:76])[N:60]([C@H:47]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:48]([N:50]2[CH2:55][CH2:54][CH2:53][C@@H:52]([CH2:56][N:57]([CH3:59])[CH3:58])[CH2:51]2)=[O:49])[CH3:77])[CH2:63][C:4]2[CH:5]=[CH:6][C:79]3[C:34](=[CH:39][CH:38]=[CH:37][CH:78]=3)[CH:35]=2)[CH3:65])[CH2:29][CH2:88][CH2:28]1)([CH3:14])([CH3:15])[CH3:16]

Participants

9

Reactant 6

HCID 6344Dichloromethane2×HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 69758373HCID 69758373, compound

Product 1

HCID 10887168HCID 10887168, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (85 mg, 0.44 mmol) was added to a solution of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (113 mg, 0.44 mmol) and 1-hydroxy-7-azabenzotriazole (60 mg, 0.44 mmol) in dichloromethane (5 ml) and N,N-dimethylformamide (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-N-[(1R)-1-benzyl-2-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methyl-2-(methylamino)-(2-naphthyl)propionamide (228 mg, 0.44 mmol) in dichloromethane (10 ml) and ethyldiisopropylamine (0.07 ml, 0.44 mmol) were added successively. The reaction mixture was stirred for 16 h, while i 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 314 mg of (1((2E)-3-[N-((1R)-1-{N-[(1R)-1-benzyl-2-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamoyl]allyl}cyclobutyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while i
  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-6d3df2788b3d4ffb903cc3c227ca2fcc
Source dataset
uspto-grants-2005_07
Patent number
US06919315B1

Reaction notes

Loading…