Diisopropylethylamine → HCID 11825613, compound

HRID 896912Notes

Reaction equation

HRID 896912 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: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].ON1C2N=CC=CC=2N=N1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[CH3:57][N:58]([CH3:66])[CH2:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.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:63]1[CH2:64][CH2:65][CH:60]([CH2:59][N:58]([CH3:66])[CH3:57])[CH2:61][CH2:62]1)=[O:25])[CH3:21])([CH3:14])([CH3:15])[CH3:16]

Participants

10

Reactant 6

HCID 81531DiisopropylethylamineHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7015127N-Boc-N-methyl-D-phenylalanineHCID 111372684-(Dimethylaminomethyl)piperidine

Product 1

HCID 11825613HCID 11825613, compoundYield 50.1%

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 (1.158,g, 6.04 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-phenylpropionic acid (149 g, 6.04 mmol) and 1-hydroxy-7-azabenzotriazole (0.822 g, 6.04 mmol) in dichloromethane (25 ml) and N,N-dimethylformamide (12 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the crude dihydrochloride salt of N,N-dimethyl-N-((piperidin-4-yl)methyl)amine (1.3 g, 6.04 mmol) in N,N-dimethylformamide (10 ml) and dichloromethane (5 ml) and ethyldiisopropylamine (6.2 ml, 36.25 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 organic layer was dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (100 g), using dichloromethane/methanol/25% aqueous ammonia (200:10:1) as eluent, to give 1.22 g of N-[(1R)-1-benzyl-2-(4-((dimethylamino)methyl)piperidin-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. dry with materialThe organic layer was dried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe crude product was purified by flash chromatography on silica (100 g)

Sources & evidence

ORD record
ord-85c2aa39d6014998843edf941a13476d
Source dataset
uspto-grants-2005_07
Patent number
US06919315B1

Reaction notes

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