Diisopropylethylamine → 3-(1,3-Dioxolan-2-yl)propyl 1-(4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)-carbonyl)amino)methyl)phenoxy)methyl)benzoyl)piperidine-4-carboxylate

HRID 874811Notes

Reaction equation

HRID 874811 reaction equation
[C:1]1([C@H:7]([NH:25][C:26]([O:28][C@@H:29]2[CH:34]3[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]3)[CH2:30]2)=[O:27])[C:8]2[CH:9]=[C:10]([CH:22]=[CH:23][CH:24]=2)[O:11][CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH:71]1[CH2:76][CH2:75][CH:74]([C:77]([O:79][CH2:80][CH2:81][CH2:82][CH:83]2[O:87][CH2:86][CH2:85][O:84]2)=[O:78])[CH2:73][CH2:72]1>CN(C=O)C.C(OCC)(=O)C>[C:1]1([C@H:7]([NH:25][C:26]([O:28][C@@H:29]2[CH:34]3[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]3)[CH2:30]2)=[O:27])[C:8]2[CH:9]=[C:10]([CH:22]=[CH:23][CH:24]=2)[O:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([N:71]3[CH2:76][CH2:75][CH:74]([C:77]([O:79][CH2:80][CH2:81][CH2:82][CH:83]4[O:84][CH2:85][CH2:86][O:87]4)=[O:78])[CH2:73][CH2:72]3)=[O:18])=[CH:20][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867208154-((3-((S)-Phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)-phenoxy)methyl)benzoic acidHCID 867223013-(1,3-Dioxolan-2-yl)propyl piperidine-4-carboxylate hydrochloride

Product 1

HCID 867223033-(1,3-Dioxolan-2-yl)propyl 1-(4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)-carbonyl)amino)methyl)phenoxy)methyl)benzoyl)piperidine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoic acid (0.300 g, 0.57 mmol) in DMF (2.5 mL) was added di-iso-propylethylamine (0.40 mL, 2.29 mmol) and HATU (0.262 g, 0.69 mmol) and the mixture stirred at RT for 30 minutes. To the resultant solution was added a solution of 3-(1,3-dioxolan-2-yl)propyl piperidine-4-carboxylate hydrochloride (0.241 g, 0.86 mmol) in DMF (1.8 mL). The mixture was stirred at RT for 18 hours. The mixture was diluted with ethyl acetate, washed with 10% aqueous potassium carbonate, brine (×2), dried (magnesium sulfate), filtered and the solvent evaporated at reduced pressure. The residue was used directly in the next step with no further purification.

Workup

  1. stirringThe mixture was stirred at RT for 18 hours
  2. washwashed with 10% aqueous potassium carbonate, brine (×2)
  3. dry with materialdried (magnesium sulfate)
  4. filtrationfiltered
  5. customthe solvent evaporated at reduced pressure
  6. customThe residue was used directly in the next step with no further purification

Sources & evidence

ORD record
ord-8b8aa91656ed4a8494a2e8c2ab8a2e68
Source dataset
uspto-grants-2015_03
Patent number
US08980913B2

Reaction notes

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