1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86680513, compound

HRID 1184594Notes

Reaction equation

HRID 1184594 reaction equation
[CH2:1]=[C:2]([C:4]1[N:5]=[CH:6][C:7]([O:10][C@H:11]2[CH2:19][N:14]3[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]3[CH2:12]2)=[N:8][CH:9]=1)[CH3:3].[F:20][C:21]([F:33])([F:32])[C:22]1[CH:23]=[C:24]([CH2:28][C:29](O)=[O:30])[CH:25]=[CH:26][CH:27]=1.O.N1(O)C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>ClCCl>[CH2:1]=[C:2]([C:4]1[N:5]=[CH:6][C:7]([O:10][C@H:11]2[CH2:19][N:14]3[CH2:15][CH2:16][N:17]([C:29](=[O:30])[CH2:28][C:24]4[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([F:32])([F:20])[F:33])[CH:23]=4)[CH2:18][C@@H:13]3[CH2:12]2)=[N:8][CH:9]=1)[CH3:3]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 86680459HCID 86680459, compound

Product 1

HCID 86680513HCID 86680513, compoundYield 57.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product from Example 152C (102 mg, 0.392 mmol) was dissolved in dichloromethane (1 mL) followed by addition of 3-trifluoromethylphenylacetic acid (88 mg, 0.431 mmol) and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (66.0 mg, 0.431 mmol). The mixture was stirred for 5 minutes and then N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (76 μL, 0.431 mmol) was added. After stirring for 18 hours at ambient temperature, the mixture was partitioned between water and dichloromethane. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on a 24 g silica gel column, eluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes and then a gradient to 10% methanol (2 N ammonia) in dichloromethane to afford the title compound as a viscous colorless oil (101 mg, 57.7%). 1H NMR (300 MHz, CDCl3) δ ppm 1.76-2.15 (m, 2H), 2.18 (s, 3H), 2.19-2.37 (m, 2H), 2.37-2.53 (m, 1H), 2.69-2.91 (m, 1H), 2.91-3.05 (m, 1H), 3.14-3.29 (m, 1H), 3.65-3.78 (m, 1H), 3.80 (d, J=3.3 Hz, 2H), 3.93 (dd, J=12.5, 2.0 Hz, 1H), 4.64 (ddd, J=10.3, 5.9, 4.5 Hz, 1H), 4.74-4.83 (m, 1H), 5.23 (d, J=1.4 Hz, 1H), 5.39 (tdd, J=7.2, 5.2, 1.9 Hz, 1H), 5.80 (s, 1H), 7.49 (ddd, J=16.3, 4.6, 2.8 Hz, 3H), 8.14 (t, J=1.4 Hz, 1H), 8.18-8.23 (m, 1H); MS (ESI) m/z 447 (M+H)+.

Workup

  1. stirringAfter stirring for 18 hours at ambient temperature
  2. customthe mixture was partitioned between water and dichloromethane
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on a 24 g silica gel column
  7. washeluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes

Sources & evidence

ORD record
ord-d77f39bb0c7a446cb47fc0d99eef46fe
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

Loading…