Diisopropylethylamine → Methyl 3-(4-{[4-(4-{[3-(3,3-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-1-piperidinyl]carbonyl}-1-naphthalenyl)propanoate

HRID 1669737Notes

Reaction equation

HRID 1669737 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([OH:18])=O)=[CH:8][CH:7]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.Cl.Cl.[CH3:55][C:56]1([CH3:78])[CH2:61][CH2:60][CH2:59][N:58]([CH2:62][CH2:63][CH2:64][O:65][C:66]2[CH:71]=[CH:70][C:69]([CH:72]3[CH2:77][CH2:76][NH:75][CH2:74][CH2:73]3)=[CH:68][CH:67]=2)[CH2:57]1>CN(C=O)C>[CH3:55][C:56]1([CH3:78])[CH2:61][CH2:60][CH2:59][N:58]([CH2:62][CH2:63][CH2:64][O:65][C:66]2[CH:67]=[CH:68][C:69]([CH:72]3[CH2:73][CH2:74][N:75]([C:16]([C:9]4[C:10]5[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=5)[C:6]([CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:19])=[CH:7][CH:8]=4)=[O:18])[CH2:76][CH2:77]3)=[CH:70][CH:71]=2)[CH2:57]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673464244-[3-(Methyloxy)-3-oxopropyl]-1-naphthalenecarboxylic acid2×HCID 673472063,3-Dimethyl-1-(3-{[4-(4-piperidinyl)phenyl]oxy}propyl)piperidine dihydrochloride2×

Product 1

HCID 67347576Methyl 3-(4-{[4-(4-{[3-(3,3-dimethyl-1-piperidinyl)propyl]oxy}phenyl)-1-piperidinyl]carbonyl}-1-naphthalenyl)propanoateYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-[3-(methyloxy)-3-oxopropyl]-1-naphthalenecarboxylic acid (for example as prepared for Intermediate 6) (0.197 g, 0.76 mmol) in anhydrous DMF (2 ml) was treated with HBTU (0.29 g 0.77 mmol), diisopropylethylamine (0.6 ml, 3.82 mmol), the mixture was stirred at room temperature for 20 minutes, 3,3-dimethyl-1-(3-{[4-(4-piperidinyl)phenyl]oxy}propyl)piperidine dihydrochloride (for example as prepared for Intermediate 4) (250 mg, 0.63 mmol) was added and the mixture stirred at room temperature for 4 h. The mixture was evaporated to dryness and purified on a SCX-2 cartridge (5 g) eluting with MeOH, followed by 2M ammonia solution in methanol to afford the title compound (238 mg). LCMS RT=2.79 min, ES+ve m/z 571.

Workup

  1. stirringthe mixture stirred at room temperature for 4 h
  2. customThe mixture was evaporated to dryness
  3. custompurified on a SCX-2 cartridge (5 g)
  4. washeluting with MeOH

Sources & evidence

ORD record
ord-94421fdc0c6748f8bfcae9126604b550
Source dataset
uspto-grants-2011_08
Patent number
US07989629B2

Reaction notes

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