1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68651900, compound

HRID 646775Notes

Reaction equation

HRID 646775 reaction equation
[NH2:1][C:2]1[C:3]([C:26](O)=[O:27])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][C@H:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1.[NH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]([NH2:36])[CH2:30]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>>[NH2:1][C:2]1[C:3]([C:26]([NH:36][CH:31]2[CH2:32][CH2:33][CH2:34][CH2:35][NH:29][CH2:30]2)=[O:27])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][C@@H:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[O:15])[CH:9]=2)=[CH:6][N:7]=1

Participants

5

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2756445Azepan-3-amineHCID 68651967HCID 68651967, compound

Product 1

HCID 68651900HCID 68651900, compoundYield 4.3%

Procedure

To a solution of 3-amino-6-(3-{[(1R)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxylic acid (409 mg, 1.09 mmol) were added azepan-3-amine (125 mg, 1.09 mmol), EDCI (252 mg, 1.31 mmol), HOBt (178 mg, 1.31 mmol) at ambient temperature. After being stirred for 2 h, the reaction mixture was quenched by addition of aqueous sodium bicarbonate followed by extraction with ethyl acetate (20 mL×3). The aqueous phase was extracted once with additional ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo gave a crude oil, which was purified by preparative HPLC to yield the 3-amino-N-azepan-3-yl-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]carbonyl}phenyl)pyrazine-2-carboxamide (22 mg, 4.2% yield): 1H NMR (400 MHz, CD3OD): δ 8.70 (m, 1H), 8.67 (m, 1H), 8.27 (m, 1H) 7.97 (m, 1H), 7.62 (t, 1H), 7.25 (m, 4H), 5.70 (m, 1H), 4.99 (m, 1H), 4.43 (m, 1H), 3.46 (m, 2H), 3.38 (m, 1H), 3.15 (m, 2H), 2.94 (m, 1H), 2.61 (m, 1H), 2.17 (m, 2H), 1.95 (m, 4H), 1.62 (m, 1H); MS (EI) for C27H30N6O2: 471.32 (MH+).

Workup

  1. customthe reaction mixture was quenched by addition of aqueous sodium bicarbonate
  2. extractionfollowed by extraction with ethyl acetate (20 mL×3)
  3. extractionThe aqueous phase was extracted once with additional ethyl acetate
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride
  5. dry with materialthen dried over anhydrous magnesium sulfate
  6. filtrationFiltration and concentration in vacuo
  7. customgave a crude oil, which
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-0f1e8f1993dd4266803c786a120fdeb4
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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