3-Chlorobenzoic Acid → HCID 68048116, compound

HRID 1408870Notes

Reaction equation

HRID 1408870 reaction equation
Cl.Cl.[C:3]12([NH2:12])[CH2:10][C:7]([NH2:11])([CH2:8][CH2:9]1)[CH2:6][CH2:5][CH2:4]2.[CH3:13][C:14]1[N:19]=[C:18]([C:20]([OH:22])=O)[CH:17]=[CH:16][CH:15]=1.[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([OH:29])=[O:28].C([N:35](CC)CC)C.Cl.CN(C)CCCN=C=NCC>CN(C)C1C=CN=CC=1.ClCCl>[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([NH:11][C:7]12[CH2:10][C:3]([NH:12][C:20]([C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:13])[N:19]=3)=[O:22])([CH2:9][CH2:8]1)[CH2:4][CH2:5][CH2:6]2)=[O:28].[C:3]12([NH:12][C:20](=[O:22])[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:13])[N:19]=3)[CH2:10][C:7]([NH:11][C:27](=[O:29])[C:26]3[CH:30]=[CH:31][CH:32]=[C:24]([CH3:25])[N:35]=3)([CH2:8][CH2:9]1)[CH2:6][CH2:5][CH2:4]2

Participants

9

Reactant 5

HCID 4473-Chlorobenzoic AcidHCID 8471TriethylamineHCID 702826-Methylpyridine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67984839HCID 67984839, compound

Product 2

HCID 57405946HCID 57405946, compoundYield 2%HCID 68048116HCID 68048116, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of bicyclo[3.2.1]octane-1,5-diamine dihydrochloride (100 mg, 0.469 mmol), 6-methylpicolinic acid (64.3 mg, 0.47 mmol) and 3-chloro-benzoic acid (73.4 mg, 0.47 mmol) in methylene chloride (10 mL, 200 mmol) was treated with triethylamine (0.66 mL, 4.69 mmol). The mixture was stirred for a few minutes. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (360 mg, 1.88 mmol) and 4-dimethylaminopyridine (11.5 mg, 0.0938 mmol) were added. The reaction mixture was stirred at rt overnight. The reaction was diluted with a small amount of dichloromethane and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified on a reversed phase liquid chromatography/mass spectrometry (RP-HPLC/MS) purification system (Gradient: acetonitrile in water, 25-95% in 3.6 minutes with a cycle time of 5 min. A shallow gradient of 30-58% of acetonitrile was used between 0.75-3.6 min to separate close-eluting impurities. Flow rate: 100 mL/min. Mobile phase additive: 48 mM of ammonium formate. Column: Inertsil® C18, 30×50 mm, 5 um particle size) to afford 3.0 mg (2%) of 6-methyl-pyridine-2-carboxylic acid [5-(3-chloro-benzoylamino)-bicyclo[3.2.1]oct-1-yl]-amide (Example 2) and 7.0 mg (4%) of N,N′-(bicyclo[3.2.1]octane-1,5-diyl)bis(6-methylpicolinamide) (Example 3). Analytical data were listed in Table 3.

Workup

  1. stirringThe reaction mixture was stirred at rt overnight
  2. washwashed with water
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified on a reversed phase liquid chromatography/mass spectrometry (RP-HPLC/MS) purification system (Gradient
  7. waitA shallow gradient of 30-58% of acetonitrile was used between 0.75-3.6 min
  8. customto separate
  9. washclose-eluting impurities

Sources & evidence

ORD record
ord-44868ef4a8c94fbea1ed32cff83f3320
Source dataset
uspto-grants-2014_12
Patent number
US08921370B2

Reaction notes

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