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

HRID 1099478Notes

Reaction equation

HRID 1099478 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-cdafe770f5334d34a252ad68ec78b94b
Source dataset
uspto-grants-2012_03
Patent number
US08143445B2

Reaction notes

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