Diisopropylethylamine → HCID 11028487, compound

HRID 2104321Notes

Reaction equation

HRID 2104321 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][CH:51]1[CH2:56][CH2:55][N:54]([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)[CH2:53][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:54]1[CH2:55][CH2:56][CH:51]([CH2:50][N:48]([CH3:49])[CH3:47])[CH2:52][CH2:53]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 11130484HCID 11130484, compound

Product 1

HCID 11028487HCID 11028487, compoundYield 78.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (416 mg, 2.17 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propionic acid (715 mg, 2.17 mmol) and 1-hydroxy-7-azabenzotriazole (296 mg, 2.17 mmol) in dichloromethane (20 ml) and N,N-dimethylformamide (10 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-1-(4-((dimethylamino)methyl)piperidin-1-yl)-2-(methylamino)-3-phenylpropan-1-one (659 mg, 2.17 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml) and ethyldiisopropylamine (0.56 ml, 3.26 mmol) 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 (100 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml). The aqueous solution 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 (80 g), using ethyl acetate/heptane/triethylamine (1:1:0.08) as eluent, to give 1.05 g of N-((1R)-1-{N-[(1R)-1-benzyl-2-(4-((dimethylamino)methyl)piperidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic 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 (100 ml)
  4. extractionThe aqueous solution 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 (80 g)

Sources & evidence

ORD record
ord-8127f8ab78234dbf8aef4e71d9d586a5
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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