Diisopropylethylamine → HCID 11061050, compound

HRID 2104334Notes

Reaction equation

HRID 2104334 reaction equation
Cl.[CH3:2][N:3]([CH3:12])[CH2:4][CH2:5][CH2:6]N=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](O)=[O:24])[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.CN([CH2:50][C@@H:51]1CCC[N:52]1[C:56](=[O:67])[C@H:57]([NH:65][CH3:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)C.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:24])[N:65]([C@H:57]([CH2:58][C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1)[C:56]([N:52]1[CH2:51][CH2:50][CH2:6][C@H:5]1[CH2:4][N:3]([CH3:2])[CH3:12])=[O:67])[CH3:66])[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])([CH3:14])([CH3:15])[CH3:16]

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 11098231HCID 11098231, compound

Product 1

HCID 11061050HCID 11061050, compoundYield 82.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (530 mg, 2.76 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propionic acid (911 mg, 2.76 mmol) and 1-hydroxy-7-azabenzotriazole (376 mg, 2.76 mmol) in dichloromethane (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-1-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-methylamino-3-phenylpropan-1-one (800 mg, 2.76 mmol) in dichloromethane (5 ml) and N,N-dimethylformamide (5 ml) and ethyldiisopropylamine (0.71 ml, 4.15 mmol) were added successively. The reaction mixture was stirred for 3 days, 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 (3×70 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 (200:10:1) as eluent, to give 1.37 g of N-((1R)-1-{N-[(1R)-1-benzyl-2-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 3 days, 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 (3×70 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 (90 g)

Sources & evidence

ORD record
ord-25c04ba9926e41228c9e5fc0c5b08cff
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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