1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 131733536, compound

HRID 2284842Notes

Reaction equation

HRID 2284842 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]([OH:19])=[O:18])=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:37][C:38]1[CH:39]=[N+:40]([O-:58])[CH:41]=[C:42]([Cl:57])[C:43]=1[CH2:44][C@@H:45]([C:47]1[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[C:49]([O:55][CH3:56])[CH:48]=1)O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:57][C:42]1[CH:41]=[N+:40]([O-:58])[CH:39]=[C:38]([Cl:37])[C:43]=1[CH2:44][C@H:45]([O:18][C:17](=[O:19])[C:16]1[CH:15]=[CH:14][C:13]([CH2:12][O:11][C:10]2[CH:22]=[CH:23][CH:24]=[C:8]([C@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[NH:25][C:26]([O:28][C@@H:29]3[CH:34]4[CH2:35][CH2:36][N:31]([CH2:32][CH2:33]4)[CH2:30]3)=[O:27])[CH:9]=2)=[CH:21][CH:20]=1)[C:47]1[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[C:49]([O:55][CH3:56])[CH:48]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 71092494(S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 867208154-((3-((S)-Phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)-phenoxy)methyl)benzoic acid

Product 1

HCID 131733536HCID 131733536, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 4-((3-((S)-Phenyl((((R)-quinuclidin-3-yloxy)carbonyl)-amino)methyl)phenoxy)methyl)-benzoic acid (I17, 243 mg, 0.5 mmol) in DMF (2 mL) was added a solution of (1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)-ethanol (172 mg, 0.5 mmol) in DMF (5 mL), followed by DMAP (31 mg, 0.25 mmol) and EDC.HCl (192 mg, 1 mmol). The mixture was allowed to stir at room temperature for 18 h and then the solvent was removed in vacuo. The residue was partitioned between DCM (15 mL) and saturated sodium bicarbonate solution (15 mL). The organic phase was washed with brine (15 mL), passed through a hydrophobic frit and the solvent was removed in vacuo. Purification was achieved by preparative HPLC to afford the title compound as a white solid (169 mg, 42%). 1H NMR (400 MHz, DMSO): δ 8.58 (s, 2 H), 8.27 (s, 1 H), 8.02 (d, J=8.1 Hz, 2 H), 7.59 (d, J=8.0 Hz, 2 H), 7.36-7.19 (m, 6 H), 7.10-6.88 (m, 6 H), 6.25 (dd, J=9.5, 4.4 Hz, 1 H), 5.84 (d, J=9.4 Hz, 1 H), 5.20 (s, 2 H), 4.64-4.57 (m, 1 H), 3.81 (s, 3 H), 3.78 (s, 3 H), 3.67 (dd, J=14.7, 9.7 Hz, 1 H), 3.37 (dd, J=14.1, 4.2 Hz, 1 H), 3.14 (t, J=11.7 Hz, 1 H), 2.83-2.52 (m, 5 H), 1.98-1.90 (m, 1 H), 1.88-1.76 (m, 1 H), 1.69-1.57 (m, 1 H), 1.57-1.44 (m, 1 H), 1.44-1.32 (m, 1 H). LCMS (Method 1): [MH+]=812 at 2.97 min.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was partitioned between DCM (15 mL) and saturated sodium bicarbonate solution (15 mL)
  3. washThe organic phase was washed with brine (15 mL)
  4. customthe solvent was removed in vacuo
  5. customPurification

Sources & evidence

ORD record
ord-79f71404a2fd4542a0404bb3759b524f
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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