Triethylamine → {3-[(5-Formyl-2,4-dimethyl-1H-pyrrole-3-carbonyl)-amino]-propyl}-carbamic acid tert-butyl ester

HRID 1695101Notes

Reaction equation

HRID 1695101 reaction equation
[CH:1]([C:3]1N[N:6]([CH3:8])[CH:5]([C:9]([OH:11])=O)[C:4]=1[CH3:12])=[O:2].[CH3:13]N(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[C:42]([NH:49][CH2:50][CH2:51][CH2:52][NH2:53])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].C(=O)(O)[O-].[Na+].[OH-].[Na+]>CN(C)C=O.[Cl-].[Na+].O.O>[C:45]([O:44][C:42](=[O:43])[NH:49][CH2:50][CH2:51][CH2:52][NH:53][C:1]([C:3]1[C:4]([CH3:12])=[C:5]([CH:9]=[O:11])[NH:6][C:8]=1[CH3:13])=[O:2])([CH3:46])([CH3:47])[CH3:48]

Participants

11

Reactant 7

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516892Sodium BicarbonateHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 27960291-Hydroxybenzotriazole hydrateHCID 86633707HCID 86633707, compound

Product 1

HCID 86633706{3-[(5-Formyl-2,4-dimethyl-1H-pyrrole-3-carbonyl)-amino]-propyl}-carbamic acid tert-butyl esterYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 5-formyl-2,4-dimethyl-1H-pyrazol-3-carboxylic acid (0.300 g, 1.79 mmol), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (0.516 g, 2.69 mmol), 1-Hydroxybenzotriazole hydrate (0.364 g, 2.69 mmol), triethylamine (0.502 ml, 3.56 mmol) in dimethylformamide (3 ml) was added N-Boc-1,3-diaminopropane (0.375 ml, 2.15 mmol). The solution was stirred at room temperature for 15 hours. A mixture of brine (1.5 ml), water (1.5 ml) and saturated aqueous sodium bicarbonate (1.5 ml) was added and the pH of the solution adjusted to 12 by addition of 10N sodium hydroxide. The solution was extracted 3 times with a mixture of dichloromethane:Methanol (9:1). The organic layer was dried with anhydrous magnesium sulfate. The solvent was removed and the residue purified by flash chromatography (Hexane:Ethyl acetate (50 to 100%)) to yield the desired compound as a yellow solid (0.30 g, 52%). 1H NMR (400 MHz, DMSO-d6) δ 11.90 (s, 1H); 9.50 (s, 1H); 7.50 (m, 1H); 6.90 (m, 1H); 3.20 (q, 2H); 3.00 (q, 2H); 2.30 (s, 3H)); 2.20 (s, 3H)); 1.60 (m, 2H)); 1.40 (s, 9H). LCMS: method D, RT=2.103 min, [M+Na+=346], and [M−Boc+Na+=246].

Workup

  1. additionwas added
  2. extractionThe solution was extracted 3 times
  3. additionwith a mixture of dichloromethane:Methanol (9:1)
  4. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  5. customThe solvent was removed
  6. customthe residue purified by flash chromatography (Hexane:Ethyl acetate (50 to 100%))

Sources & evidence

ORD record
ord-f41799ac7033432aa72eb77a61dadb14
Source dataset
uspto-grants-2012_04
Patent number
US08163511B2

Reaction notes

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