Diisopropylethylamine → HCID 59694118, compound

HRID 1624346Notes

Reaction equation

HRID 1624346 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[NH:43]1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[N:45]=[C:44]1[CH2:52][N:53]([CH:58]1[C:67]2[N:66]=[CH:65][CH:64]=[CH:63][C:62]=2[CH2:61][CH2:60][CH2:59]1)[CH2:54][CH2:55][CH2:56][NH2:57]>CN(C=O)C.C(OCC)(=O)C.O>[NH:43]1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[N:45]=[C:44]1[CH2:52][N:53]([CH:58]1[C:67]2[N:66]=[CH:65][CH:64]=[CH:63][C:62]=2[CH2:61][CH2:60][CH2:59]1)[CH2:54][CH2:55][CH2:56][NH:57][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Br:1])[CH:3]=[N:4][CH:5]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 887075-Bromonicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 10308735HCID 10308735, compound

Product 1

HCID 59694118HCID 59694118, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromonicotinic acid (120 mg, 0.60 mmol) in DMF (3 mL) was added 1-hydroxybenzotriazole hydrate (96 mg, 0.72 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (137 mg, 0.72 mmol), N,N-diisopropylethylamine (0.21 mL, 1.19 mmol), and N1-(1H-benzoimidazol-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-propane-1,3-diamine (200 mg, 0.60 mmol). The reaction mixture was stirred at room temperature overnight. Then it was diluted with ethyl acetate (40 mL) and water (25 mL). The aqueous layer was concentrated and dried in vacuo to afford a brown oil. Purification by radial chromatography (1 mm plate, using NH4OH/CH3OH/CH2Cl2; 1:1:100→1:4:100) afforded the product as pale yellow foam (220 mg, 71%). 1H NMR (CDCl3) δ 1.59-1.85 (m, 4H), 1.99-2.03 (m, 1H), 2.16-2.20 (m, 1H), 2.58-2.62 (m, 1H), 2.73-2.85 (m, 3H), 3.27-3.34 (m, 1H), 3.50-3.54 (m, 1H), 3.95 (d, 2H, J=2.4 Hz), 4.03-4.08 (m, 1H), 7.09-7.16 (m, 3H), 7.31 (br s, 1H), 7.42 (d, 1H, J=7.5 Hz), 7.58 (br s, 1H), 7.91 (t, 1H, J=5.7 Hz), 8.07 (t, 1H, J=2.1 Hz), 8.40 (d, 1H, J=3.6 Hz), 8.64 (d, 1H, J=2.4 Hz), 8.74 (d, 1H, J=1.8 Hz).

Workup

  1. concentrationThe aqueous layer was concentrated
  2. customdried in vacuo
  3. customto afford a brown oil
  4. customPurification by radial chromatography (1 mm plate, using NH4OH/CH3OH/CH2Cl2; 1:1:100→1:4:100)

Sources & evidence

ORD record
ord-a91f0e9dc4af42b3bb718c8c3070f4d1
Source dataset
uspto-grants-2014_07
Patent number
US08778967B2

Reaction notes

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