Hydrochloric Acid → (5-(Pyridin-3-ylcarbamoyl)pentyl]carbamic acid tert-butyl ester

HRID 1255099Notes

Reaction equation

HRID 1255099 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[C:8]([O:12][C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21](O)=[O:22])=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl.CCN(C(C)C)C(C)C>C(Cl)Cl.C1C=CC2N(O)N=NC=2C=1.CCCCCC.C(Cl)CCl>[C:8]([O:12][C:13](=[O:14])[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21](=[O:22])[NH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)([CH3:11])([CH3:9])[CH3:10]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 100093-AminopyridineHCID 81531DiisopropylethylamineHCID 6376026-((tert-Butoxycarbonyl)amino)hexanoic acid

Product 1

HCID 66810297(5-(Pyridin-3-ylcarbamoyl)pentyl]carbamic acid tert-butyl esterYield 68.3%

Reagents, catalysts & solvents 4

HCID 757711-HydroxybenzotriazoleCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a mixture of 3-aminopyridine (1, 2.82 g, 30 mmole) and 6-tert-Butoxycarbonylamino-hexanoic acid (2, 9.2 g, 40 mmole) in methylene chloride (50 mL) was added HOBt (135 mg, 1 mmole), EDC. HCl (7.6 g, 40 mmole) followed by DIPEA (10.45 mL, 60 mmole). The reaction mixture was stirred at room temperature for 3 h. At this point the TLC showed the disappearance of starting material. The reaction solution was washed with water (3×25 mL), followed by aqueous sodium bicarbonate (25 mL), then brine and finally dried over anhydrous sodium sulfate, filtered and concentrated. The crude residue was purified by column chromatography using 1% methanol in methylene chloride as the eluant to give the pure product as an oily residue. This residue on trituration with hexane gave 3 as a colorless solid (6.3 g, 68%, mp 96-98° C.). 1H NMR (CDCl3) δ 8.68 (br s, 2H), 8.48 (m, 1H), 8.30 (m, 2H), 7.32 (m, 1H), 4.62 (br s, 1H), 3.16 (m, 2H), 2.40 (m, 2H), 2.78 (m, 2H), 1.50 (m, 4H), 1.40 (s, 9H).

Workup

  1. washThe reaction solution was washed with water (3×25 mL)
  2. dry with materialbrine and finally dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by column chromatography
  6. customto give the pure product as an oily residue

Sources & evidence

ORD record
ord-5491f1f0a2a4470392407f443c78f46f
Source dataset
uspto-grants-2013_06
Patent number
US08455688B2

Reaction notes

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