Diisopropylethylamine → HCID 10992766, compound

HRID 2104332Notes

Reaction equation

HRID 2104332 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:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23]([OH:25])=O)[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].O[N:34]1[C:38]2N=CC=C[C:37]=2N=N1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.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]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23]([N:34]1[CH2:38][CH2:37][CH2:6][C@H:5]1[CH2:4][N:3]([CH3:2])[CH3:12])=[O:25])[CH3:21])([CH3:14])([CH3:15])[CH3:16]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7015127N-Boc-N-methyl-D-phenylalanine

Product 1

HCID 10992766HCID 10992766, compoundYield 85.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.30 g, 6.76 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-phenylpropionic acid (1.89 g, 6.76 mmol) and 1-hydroxy-7-azabenzotriazole 0.92 g, 6.76 mmol) in dichloromethane (10 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the crude dihydrochloride salt of N-dimethyl-N-(((2S)-pyrrolidin-2-yl)methyl)amine (1.36 g, 6.76 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (10 ml) and ethyldiisopropylamine (5.75 ml, 33.8 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 phase was extracted with ethyl acetate (3×80 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 2.26 g of N-[(1R)-1-benzyl-2-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-oxoethyl]-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 phase was extracted with ethyl acetate (3×80 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-3ec0227ab3cd4cf5b0c46eae186ead48
Source dataset
uspto-grants-2009_08
Patent number
US07576062B2

Reaction notes

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