Diisopropylethylamine → di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

HRID 2105020Notes

Reaction equation

HRID 2105020 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:26](Cl)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.CCN(C(C)C)C(C)C.[NH2:48][C:49]1[CH:50]=[C:51]2[C:56](=[CH:57][CH:58]=1)[C:55]([N:59]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[N:54][CH:53]=[CH:52]2>CC#N.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[N:3]=[C:4]([CH:26]([NH:48][C:49]2[CH:50]=[C:51]3[C:56](=[CH:57][CH:58]=2)[C:55]([N:59]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:67]([O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:68])=[N:54][CH:53]=[CH:52]3)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 688168844-bromo-2-(chloro(5-ethyl-2-fluoro-3-methoxyphenyl)methyl)-1-trityl-1H-imidazole

Product 1

HCID 86607941di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonateYield 78.4%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of the chloro intermediate (350 mg, 0.594 mmol) in 5 mL CH3CN and 2 mL CH2Cl2 at rt, was added DIEA (0.207 mL, 1.19 mmol), di-tert-butyl (6-aminoisoquinolin-1-yl)imidodicarbonate (235 mg, 0.653 mmol). The mixture was stirred at rt for 18 h and at 40° C. for 3 h, then was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 425 mg of Intermediate 206.4 as a colorless residue.

Workup

  1. washThe organic phase was washed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-ccd74af2b5864045b4ebd8df98b32efb
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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