Diisopropylethylamine → HCID 10930141, compound

HRID 2104327Notes

Reaction equation

HRID 2104327 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]([C@H:22]([CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[C:23]([OH:25])=O)[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH3:47][N:48]([CH2:50][C@@H:51]1[CH2:56][CH2:55][CH2:54][N:53]([C:57](=[O:68])[C@H:58]([NH:66][CH3:67])[CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH2:52]1)[CH3:49].C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[N:20]([C@@H:22]([C:23](=[O:25])[N:66]([C@H:58]([CH2:59][C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1)[C:57]([N:53]1[CH2:54][CH2:55][CH2:56][C@@H:51]([CH2:50][N:48]([CH3:49])[CH3:47])[CH2:52]1)=[O:68])[CH3:67])[CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[CH3:21])([CH3:16])([CH3:15])[CH3:14]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 11001175HCID 11001175, compound

Product 1

HCID 10930141HCID 10930141, compoundYield 96.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (379 mg, 1.98 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propionic acid (651 mg, 1.98 mmol) and 1-hydroxy-7-azabenzotriazole (269 mg, 1.98 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-1-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-methylamino-3-phenylpropan-1-one (600 mg, 1.98 mmol) in dichloromethane (10 ml) and ethyldiisopropylamine (0.51 ml, 2.97 mmol) were added successively. The reaction mixture was stirred for 3 days, while it was warming up to room temperature. Ethyl acetate (100 ml) was added. The solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (100 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 (90 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 1.18 g of N-((1R)-1-{N-[(1R)-1-benzyl-2-((3S)-3-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

Workup

  1. customAt 0° C
  2. stirringThe reaction mixture was stirred for 3 days, while it
  3. temperaturewas warming up to room temperature
  4. washThe solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml)
  5. extractionThe aqueous phase was extracted with ethyl acetate (3×50 ml)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (90 g)

Sources & evidence

ORD record
ord-4119e5a800464c77a87204653d478dc6
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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