Triethylamine → tert-butyl 2-(2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)-N-(3-nitrobenzyl)acetamido)acetate

HRID 735631Notes

Reaction equation

HRID 735631 reaction equation
CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.[C:29]([O:33][C:34]([N:36]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[C:37]1[C:46]2[C:41](=[CH:42][C:43]([NH:47][CH:48]([C:52]3[CH:57]=[C:56]([CH3:58])[C:55]([CH2:59][CH2:60][OH:61])=[C:54]([CH3:62])[CH:53]=3)[C:49]([OH:51])=O)=[CH:44][CH:45]=2)[CH:40]=[CH:39][N:38]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].[N+:70]([C:73]1[CH:74]=[C:75]([CH:86]=[CH:87][CH:88]=1)[CH2:76][NH:77][CH2:78][C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])([O-:72])=[O:71]>CCOC(C)=O>[C:29]([O:33][C:34]([N:36]([C:63]([O:65][C:66]([CH3:68])([CH3:67])[CH3:69])=[O:64])[C:37]1[C:46]2[C:41](=[CH:42][C:43]([NH:47][CH:48]([C:52]3[CH:57]=[C:56]([CH3:58])[C:55]([CH2:59][CH2:60][OH:61])=[C:54]([CH3:62])[CH:53]=3)[C:49]([N:77]([CH2:78][C:79]([O:81][C:82]([CH3:85])([CH3:84])[CH3:83])=[O:80])[CH2:76][C:75]3[CH:86]=[CH:87][CH:88]=[C:73]([N+:70]([O-:72])=[O:71])[CH:74]=3)=[O:51])=[CH:44][CH:45]=2)[CH:40]=[CH:39][N:38]=1)=[O:35])([CH3:31])([CH3:32])[CH3:30]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 578427352-(1-(Bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)acetic acidHCID 57842741Tert-butyl 2-(3-nitrobenzylamino)acetate

Product 1

HCID 57842583tert-butyl 2-(2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)-N-(3-nitrobenzyl)acetamido)acetateYield 42.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

EDCI (142 mg, 0.74), HOAt (101 mg, 0.74 mmol), and triethylamine (0.18 mL, 1.35 mmol) were added to a solution of 50C (380 mg, 0.67 mmol) and 52C (197 mg, 0.74 mmol) in that order. The reaction mixture was stirred at 60° C. for 3 h. The solution was diluted with EtOAc, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude solid was purified by flash chromatography (0% to 100% EtOAc in hexanes) to afford 52D (230 mg, 42%) as a yellow solid. MS (ESI) m/z 814.9 (M+H)+.

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude solid was purified by flash chromatography (0% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a3d53fc1bb7f4aaaa41c039c9ab9ef43
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

Loading…