Diisopropylethylamine → (4-{4-[(1H-Imidazol-2-yl-carbamoyl)methoxy]phenyl}butyl)carbamic acid tert-butyl ester

HRID 132568

Reaction equation

HRID 132568 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:23]=[CH:22][C:16]([O:17][CH2:18][C:19]([OH:21])=O)=[CH:15][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl.S(O)(O)(=O)=O.[NH2:60][C:61]1[NH:62][CH:63]=[CH:64][N:65]=1>C1COCC1.CN(C1C=CN=CC=1)C.CC#N.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([O:17][CH2:18][C:19](=[O:21])[NH:60][C:61]2[NH:62][CH:63]=[CH:64][N:65]=2)=[CH:22][CH:23]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 5

HCID 81531DiisopropylethylamineHCID 135136Bis(2-amino-1H-imidazole) sulphateHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22054428[4-(4-tert-Butoxycarbonylaminobutyl)phenoxy]acetic acid

Product 1

HCID 21031134(4-{4-[(1H-Imidazol-2-yl-carbamoyl)methoxy]phenyl}butyl)carbamic acid tert-butyl esterYield 66.5%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

[4-(4-tert-Butoxycarbonylaminobutyl)phenoxy]acetic acid 33 (1.19 g, 3.68 mmol) was dissolved in anhydrous THF (10 mL), CH2Cl2 (10 mL) and CH3CN (5 mL). To the solution were sequentially added HOAt (200 mg, 1.47 mmol), DMAP (135 mg, 1.10 mmol), and diisopropylethylamine (3.2 mL, 18.40 mmol), followed by the addition of EDC-HCl (1.03 g, 5.35 mmol). The reaction mixture was stirred at room temperature for 15 min. Amino imidazole sulfate (583 mg, 4.41 mmol) was then added and stirring was continued for 48 h. Solvents were removed by rotary evaporation. The residue was taken up in CH2Cl2 (250 mL), washed with water and brine, and concentrated under reduced pressure. Flash silica gel column chromatography eluting with methanol/dichloromethane (1:30, 1:20, v/v) gave the desired amide as a white solid (0.95 g, 66% yield). 1H NMR (300 MHz, CD3OD) δ 1.40 (s, 9H), 1.42-1.70 (m, 4H), 2.48-2.60 (m, 2H), 3.00-3.20 (m, 2H), 4.65 (s, 2H), 6.79-6.89 (m, 4H), 7.10 (d, 2H). m/z (ESI): 389 [C20H28N4O4+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 48 h
  3. customSolvents were removed by rotary evaporation
  4. washwashed with water and brine
  5. concentrationconcentrated under reduced pressure
  6. washFlash silica gel column chromatography eluting with methanol/dichloromethane (1:30, 1:20, v/v)

Sources & evidence

ORD record
ord-8ac4c7d1aa93444b975ad1b799afc8eb
Source dataset
uspto-grants-2008_06
Patent number
US07388013B2

Linked notes

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