1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 58084376, compound

HRID 2174658Notes

Reaction equation

HRID 2174658 reaction equation
[NH2:1][C:2]1[C:3]([C:20](O)=[O:21])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.Cl.[CH3:24][O:25][NH:26][CH3:27].O.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.C(N=C=NCCCN(C)C)C>C1COCC1>[NH2:1][C:2]1[C:3]([C:20]([N:26]([O:25][CH3:24])[CH3:27])=[O:21])=[N:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:12][CH:13]=2)=[CH:6][N:7]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 58084374HCID 58084374, compound

Product 1

HCID 58084376HCID 58084376, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-6-(4-isopropylsulfonylphenyl)pyrazine-2-carboxylic acid (10 g, 31.12 mmol) was dissolved in THF (80 mL) and cooled to 0° C. N-methoxymethanamine hydrochloride (3.642 g, 37.34 mmol), 1-hydroxybenzotriazole hydrate (5.242 g, 34.23 mmol), DIPEA (8.044 g, 10.84 mL, 62.24 mmol) and 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine (5.314 g, 34.23 mmol) was added and the reaction mixture allowed to warm to ambient temperature over 15 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in EtOAc. The organic layer was washed water (×2), saturated aqueous NaHCO3 (×2) and brine (×1). The organic layer was dried (MgSO4), filtered and concentrated in vacuo and the residue purified by column chromatography (eluting with 30% EtOAc/petroleum ether) to give the sub-title compound as an off-white solid (8.8 g, 78% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.18 (d, 6H), 3.42 (s, 3H), 3.44 (sept, 1H), 3.67 (s, 3H), 6.95 (br s, 2H), 7.90 (d, 2H), 8.22 (d, 2H) and 8.82 (s, 1H) ppm; (ES+) 366.1.

Workup

  1. temperatureto warm to ambient temperature over 15 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in EtOAc
  4. washThe organic layer was washed water (×2), saturated aqueous NaHCO3 (×2) and brine (×1)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by column chromatography (eluting with 30% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-7f25ef56d2a74701924d7c3c6a0d4728
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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