Urea → HCID 69037509, compound

HRID 1893083Notes

Reaction equation

HRID 1893083 reaction equation
[C:1]([NH:18][CH2:19][CH2:20][CH2:21]I)([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].C(Cl)Cl.[CH3:26][N:27]([CH:29]=[O:30])C.[NH2:31][C:32]([NH2:34])=O.[CH3:35][Si:36]([CH3:41])([CH3:40])[CH2:37][CH2:38]O>CC#N>[CH3:4][O:3][C:1](=[O:2])[CH:26]([NH:27][C:29](=[O:30])[CH2:38][CH2:37][Si:36]([CH3:41])([CH3:40])[CH3:35])[CH2:17][C:5]1[N:31]=[CH:32][N:34]([CH2:21][CH2:20][CH2:19][NH:18][C:1]([O:3][CH2:4][CH:5]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3[C:6]2=[CH:7][CH:8]=[CH:9][CH:10]=3)=[O:2])[CH:6]=1

Participants

6

Reactant 4

HCID 1176UreaHCID 180132-(Trimethylsilyl)ethanolHCID 11200610HCID 11200610, compoundHCID 22350042dichloromethane N,N-dimethylformamide

Product 1

HCID 69037509HCID 69037509, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A mixture of 3 (196 mg; 1.0 mmol) and N-Fmoc-3-iodopropylamine (1.22 g; 3.0 mmol) in MeCN (40 ml) was heated at reflux for 4.5 days. When compound 3, urea derivative, was not detectable by TLC, the reaction mixture was concentrated in vacuo, resulting in a white solid. The solid material was redissolved in MeCN (40 ml) and 2-trimethylsilylethanol (355 mg; 3.0 mmol) and dipea (259 mg; 2.0 mmol) were added. The resulting mixture was stirred at RT under N2 for 16 hrs. The solvent was removed in vacuo, followed by purification by column chromatography (silica; EtOAc). Yield: 316 mg (53% over two steps) of a foamy colourless solid Found: C, 62.1; H, 6.2; N, 9.5; Calc. for C31H40N4O6Si: C, 62.8; H, 6.8; N, 9.5; νmax (KBr)/cm−1 3329br NH, 1730s, 1698vs C═O; δH (300.8 MHz; CD3CN) 7.82 (2H, pseudo-d, 2×ArH), 7.64 (2H, pseudo-d, 2×ArH), 7.38 (3H, m, 2×ArH+N2CHHis), 7.32 (2H, pseudo-t, 2×ArH), 6.79 (1H, s, CHHis), 6.55 (1H, d, J 7.5, NH), 5.68 (1H, br s, NH), 4.35 (3H, overlapping m, OCH2−Fmoc+CαH), 4.22 (1H, t, J 6.6, OCH2CH−Fmoc), 4.07 (2H, m, CH2), 3.87 (2H, m, CH2), 3.60 (3H, s, OCH3), 2.99 (2H, m, CH2), 2.90 (2H, m, CβH2), 1.85 (2H, m, CH2), 0.93 (2H, m, CH2), 0.01 (s, 9H, Si—(CH3)3). δC (CD3CN; 75.47 MHz) 173.7 (C═Oester), 157.7, 157.6 (2×C═Oamide), 145.5, 142.2 (2×ArCq), 138.4 (CHis), 128.9, 128.3 (2×ArCH), 126.4 (CHis), 121.2, 118.6 (2×ArCH), 118.1 (CHis), 66.9, 63.7, 55.3, 52.7, 48.3, 44.9, 38.6, 32.1, 30.1, 18.3, 1.4 (Si(CH3)3); m/z (ESI-pos., MeOH) 343, 371, 533, 593 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4.5 days
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. customresulting in a white solid
  5. customThe solvent was removed in vacuo
  6. customfollowed by purification by column chromatography (silica; EtOAc)

Sources & evidence

ORD record
ord-f24f70c83805441bb93e221eff3f0fe4
Source dataset
uspto-grants-2013_08
Patent number
US08512675B2

Reaction notes

Loading…