1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 71603996, compound

HRID 716390Notes

Reaction equation

HRID 716390 reaction equation
[C:1]([C:5]1[CH:43]=[CH:42][C:8]([C:9]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[N:27]=[C:26]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=4)[O:25][N:24]=3)=[CH:19][CH:18]=2)[C:13](O)=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:65][CH2:66][C:67]([O:69]C(C)(C)C)=[O:68]>CN(C=O)C>[C:1]([C:5]1[CH:43]=[CH:42][C:8]([C:9]([NH:11][C@@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[N:27]=[C:26]([C:28]4[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:32][CH:33]=4)[O:25][N:24]=3)=[CH:19][CH:18]=2)[C:13]([NH:65][CH2:66][C:67]([OH:69])=[O:68])=[O:14])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 151417Glycine tert-butyl esterHCID 71603995HCID 71603995, compound2×

Product 1

HCID 71603996HCID 71603996, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared using General Procedures 7 and 8: To a solution of (S)-2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-1,2,4-oxadiazol-3-yl)phenyl) propanoic acid, Compound 2 (10.0 mg, 0.017 mmol) in anhydrous DMF (1 mL) was added HOBt (3.52 mg, 0.027 mmol) and EDCI (4.88 mg, 0.027 mmol) at RT. After 2 h, tert-butyl 2-aminoacetate (3.49 mg, 0.027 mmol) was added and the reaction mixture stirred at RT for 2 h. LCMS analysis showed complete conversion to the intermediate. The reaction mixture was partitioned between NaHCO3 aqueous (5 ml) and DCM (1 mL), the organic layer was collected and concentrated by vacuum and then was re-dissolved in 1 mL of DCM and 0.1 mL of TFA. The mixture was heated to 30° C. for 3 h. The final compound was purified by HPLC to afford 9.6 mg (88%) of (S)-2-(2-(4-(tert-butyl)benzamido)-3-(4-(5-(4-(heptyloxy)phenyl)-1,2,4-oxadiazol-3-yl)phenyl)propanamido)acetic acid. LCMS-ESI (m/z) calculated for C37H44N4O6: 640.3; no m/z observed, tR=11.51 min (Method 2). 1H NMR (400 MHz, DMSO) δ: 8.60 (d, J=8.4 Hz, 1H), 8.47 (t, J=5.7 Hz, 1H), 8.10 (d, J=8.8 Hz, 2H), 7.96 (d, J=8.2 Hz, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.57 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 4.83 (d, J=8.1 Hz, 1H), 4.09 (t, J=6.4 Hz, 2H), 3.94-3.69 (m, 2H), 3.34 (s, 2H), 3.26 (d, J=13.5 Hz, 1H), 3.15-3.01 (m, 1H), 1.83-1.65 (m, 2H), 1.50-1.15 (m, 16H), 0.87 (t, J=6.7 Hz, 3H). 13C NMR (101 MHz, DMSO) δ: 175.12, 171.58, 171.13, 167.99, 166.02, 162.54, 154.10, 142.44, 131.16, 130.02, 129.89, 127.23, 126.81, 124.91, 124.25, 115.50, 115.36, 67.97, 54.23, 40.10, 37.12, 34.57, 31.19, 30.88, 28.46, 28.37, 25.36, 22.02, 13.93.

Workup

  1. customPrepared
  2. customThe reaction mixture was partitioned between NaHCO3 aqueous (5 ml) and DCM (1 mL)
  3. customthe organic layer was collected
  4. concentrationconcentrated by vacuum
  5. dissolutionwas re-dissolved in 1 mL of DCM
  6. temperatureThe mixture was heated to 30° C. for 3 h
  7. customThe final compound was purified by HPLC

Sources & evidence

ORD record
ord-03de27f20d664170a700315239627738
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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