1-Hydroxybenzotriazole → HCID 86675735, compound

HRID 2403251Notes

Reaction equation

HRID 2403251 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:20][C:21]([NH:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:22])[CH2:16][C:17]([OH:19])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:30]([NH2:33])[C:31]#[CH:32].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([NH:20][C:21](=[O:22])[NH:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:16][C:17](=[O:19])[NH:33][CH2:30][C:31]#[CH:32])=[CH:11][CH:10]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 239041PropargylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67256317HCID 67256317, compound

Product 1

HCID 86675735HCID 86675735, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-(tert-butoxycarbonylamino)phenyl)-3-(3-(2-ethoxy-2-oxoethyl)ureido)propanoic acid (1 equivalent, 150 mg, 0.37 mmol), propargylamin hydrocholoride (1 equivalent, 33 mg, 0.37 mmol), DIPEA (2.2 equivalent, 140 μl, 0.81 mmol), and HOBt (1.2 equivalent, 60 mg, 0.45 mmol) were dissolved in 2 ml of DMF. The reaction mixture was stirred at room temperature for 20 minutes. Then EDAP (1.2 equivalent, 84 mg, 0.45 mmol) was added and the reaction mixture was stirred at room temperature overnight. The mixture was washed by 30 ml of NaHCO3, and extracted by 3×20 ml of EtOAc. The organic phase was dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography (EDP/EtOAc) to afford the compound 200 (108 mg, 66%) as a white solid, Rf=0.25 (EtOAc). 1H NMR (200 MHz, DMSO) δ 9.28 (s, 1H), 8.29 (t, J=5.2 Hz, 1H), 7.37 (d, J=8.5 Hz, 2H), 7.16 (d, J=8.5 Hz, 2H), 6.72 (d, J=8.5 Hz, 1H), 6.34 (t, J=6.1 Hz, 1H), 4.99 (q, J=7.0 Hz, 1H), 4.09 (q, J=7.2 Hz, 2H), 3.86-3.78 (m, 2H), 3.76 (d, J=5.9 Hz, 2H), 3.41-3.32 (m, 2H), 3.13-3.08 (m, 1H), 1.50 (s, 9H), 1.20 (t, J=7.1 Hz, 3H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. washThe mixture was washed by 30 ml of NaHCO3
  3. extractionextracted by 3×20 ml of EtOAc
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by flash chromatography (EDP/EtOAc)

Sources & evidence

ORD record
ord-82f04a41daf948b38536fc7bbc17a01c
Source dataset
uspto-grants-2014_08
Patent number
US08802666B2

Reaction notes

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